Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs

Srinivas V Koduru; Ashley N Leberfinger; Yuka I Kawasawa; Milind Mahajan; Niraj J Gusani; Arun J Sanyal; Dino J Ravnic

doi:10.1038/s41598-018-26360-1

. 2018 May 22;8:7967. doi: 10.1038/s41598-018-26360-1

Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs

Srinivas V Koduru ^1,^✉, Ashley N Leberfinger ¹, Yuka I Kawasawa ², Milind Mahajan ³, Niraj J Gusani ⁴, Arun J Sanyal ⁵, Dino J Ravnic ^1,^✉

PMCID: PMC5964116 PMID: 29789629

Abstract

Hepatocellular carcinoma (HCC) was the fifth leading cause of cancer death in men and eighth leading cause of death in women in the United States in 2017. In our study, we sought to identify sncRNAs in various stages of development of HCC. We obtained publicly available small RNA-seq data derived from patients with cirrhosis (n = 14), low-grade dysplastic nodules (LGDN, n = 9), high grade dysplastic nodules (HGDN, n = 6), early hepatocellular carcinoma (eHCC, n = 6), and advanced hepatocellular carcinoma (HCC, n = 20), along with healthy liver tissue samples (n = 9). All samples were analyzed for various types of non-coding RNAs using PartekFlow software. We remapped small RNA-seq to miRBase to obtain differential expressions of miRNAs and found 87 in cirrhosis, 106 in LGDN, 59 in HGDN, 80 in eHCC, and 133 in HCC. Pathway analysis of miRNAs obtained from diseased samples compared to normal samples showed signaling pathways in the microRNA dependent EMT, CD44, and others. Additionally, we analyzed the data sets for piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. We validated the in silico data using human HCC samples with NanoString miRNA global expression. Our results suggest that publically available data is a valuable resource for sncRNA identification in HCC progression (FDR set to <0.05 for all samples) and that a data mining approach is useful for biomarker development.

Introduction

Hepatocellular carcinoma (HCC) was the fifth leading cause of cancer death in men and eighth leading cause of death in women in the United States in 2017. The incidence of HCC has been increasing every year, with an estimated 40,710 new cases in 2017¹. In addition, death rates are increasing by 3% every year, with an estimated 28,920 deaths in 2017¹. These statistics suggest more research needs to be done towards understanding the biology, diagnosis, and prevention. Primary liver cancer, or HCC can be triggered by ongoing inflammation from pathologies such as cirrhosis, dysplastic nodule formation, viral infections (i.e. viral hepatitis), and NASH. Cirrhosis is a condition in which the liver becomes scarred secondary to repeated insults.

HCC often originates in a focus of dysplasia within a cirrhotic regenerative nodule. With progression to more severe dysplasia, the lesion assumes increasingly malignant characteristics until it becomes frankly cancerous. Tumors may be well differentiated or poorly differentiated. As expected, poorly differentiated HCC has a more aggressive course and poorer outcomes than well differentiated HCC.

Scientific progress in next generation sequencing (NGS) has enhanced our understanding of biological systems by profiling whole transcriptomic expression at a molecular level². Small RNAs are small non-coding RNAs (sncRNA) consisting of 17–250 nucleotides in length that perhaps play a crucial role in disease development³. A nearly comprehensive repertoire of various types of sncRNAs has been collected and analyzed including: microRNA (miRNAs, 17–22 nucleotides)⁴, piwi-interacting RNAs (piRNAs, 26–33 nucleotides)⁵, small nuclear/nucleolar RNAs (sn/snoRNAs, 70–120 nucleotides), long non-coding RNAs (lncRNAs, more than 200 nucleotides)⁶, and circular RNAs (circRNA)⁷. This has led to great interest in revealing their role in transcriptional regulation. piRNAs are the largest class of the small non-coding RNA family and are implicated in epigenetic and post-transcriptional regulation but still lack functional characterization⁸. lncRNAs are a diverse class of RNAs, believed to have an important role in cellular mechanisms; however, little biological relevance has been established thus far⁹. circRNAs are a recently rediscovered class of non-coding RNAs, which were initially described as scrambled exons^10,11. They are resistant to endonuclease treatment and are highly stable¹². snoRNAs are perhaps the most ancient and highly conserved class of sncRNAs carrying out a fundamental role in modification and processing of ribosomal RNAs (rRNA), transfer RNAs (tRNA), and small nuclear RNAs (snRNA)¹³. Two well-known classes of snoRNAs are C/D snoRNAs and box H/ACA snoRNAs which primarily differ in sequence and structure¹³.

The present study focused on in-depth analysis of small RNA sequencing data obtained from cirrhosis, low-grade dysplastic nodules (LGDN), high-grade dysplastic nodules (HGDN), early stage hepatocellular carcinoma (eHCC), and advanced stage hepatocellular carcinoma (HCC). Tissue samples were compared to healthy liver tissue. We aimed to identify the differential signature and dysregulated expression of small non-coding RNAs. We further identified the most predominantly expressed non-coding RNAs and molecular pathways that could serve as biomarkers during malignant transformation.

Materials and Methods

Read Alignment and Annotations

Healthy (BioProject: PRJNA266511) and diseased liver (BioProject: PRJEB11462) small RNA sequencing raw sample datasets¹⁴ were downloaded from NIH short read archive (SRA). The datasets contained 14 cirrhosis, 9 low-grade dysplastic nodules, 6 high-grade dysplastic nodules, 6 early HCC, and 20 advanced HCC samples along with 9 healthy liver tissue samples (normal clinical assessment and normal liver enzymes). Downloaded SRA files were converted to FASTQ files using the SRA toolkit version 2.5.7¹⁵. The FASTQ files were uploaded to PartekFlow^® software, version 6.0 (Partek, Inc., St. Louis, MO) on a Linux based High Performance Computing system at Pennsylvania State University College of Medicine, adapter-trimmed, and remapped to human genome hg19 using BWA-0.7.12 aligner (BWA-MEM) with a few modifications (mismatch penalty 2, gap open penalty 6, clipping penalty 4, and alignment score cutoff 15) for short read mapping^2,16. miRBase version 20 (http://www.mirbase.org/), which contains more than 1900 high confidence miRNAs¹⁷ was used for annotation. piRNA data was generated and annotated from piRBase (http://regulatoryrna.org/database/piRNA), which is manually curated with a focus on functional analysis¹⁸. lncRNAs were quantified using reference annotation LNCipedia (http://www.lncipedia.org) version 3.1, downloaded from all coordinates relative to the hg19 reference genome¹⁹. circRNA database (http://www.circbase.org) contains thousands of circRNAs and annotation was download and quantified²⁰. Total small RNA (including miRNA, piRNA, snRNA, snoRNA, mt-RNA, tRF3, tRF5, tRNA, and rRNA) was annotated using Gencode version 26 (www.gencodegenes.org)²¹, which provides comprehensive information on human sncRNAs. Transcript abundances were determined and expression levels were represented using normalized reads per million (RPM) values. All small RNAs with expression RPM values > 1 in 100% of the samples were considered robustly expressed and used for further analysis. Expression matrices were compared among clinicopathological features including cirrhosis, low-grade dysplastic nodules, high-grade dysplastic nodules, early stage HCC, and advanced stage HCC samples². Statistical analyses were carried out using the non-parametric Mann-Whitney U test followed by false discovery rate (FDR) correction through the Benjamini-Hochberg method. A default FDR < 0.05 was considered statistically significant²² with a log₂-fold change more than 1. Circos plots²³ were generated for differential expression of all small RNAs in various stages of liver disease.

HCC and Normal Liver Tissue Samples

Hepatocellular carcinoma (n = 3; moderately to poorly differentiated) and normal liver tissue (n = 3; adenoma) frozen samples were obtained from the Institute for Personalized Medicine (IPM) at Penn State College of Medicine, Hershey, PA, after written approval. Total RNA was extracted using a Direct-zol™ RNA Kit (Zymo Research, cat#: R2051) according to the manufacturer’s instructions. The extracted RNAs were quantified and quality checked using a NanoDrop 1000 Spectrophotometer (Thermo Fisher Scientific, Waltham, MA) and a BioAnalyzer RNA 6000 Nano Kit (Agilent Technologies, Santa Clara, CA).

MicroRNA Profiling Using NanoString nCounter miRNA Assays

Total RNA samples were analyzed according to manufacturer’s instructions for the nCounter miRNA Expression Assay kit (NanoString Technologies®, Seattle, WA). Briefly, 100 ng of each sample total RNA was used for nCounter Human miRNA sample preparation. Hybridization was conducted for 16 h at 65°C. Subsequently, probes were purified and counted on the nCounter Prep Station. Each sample was scanned for 600 FOV (fields of view) on the nCounter Digital Analyzer. Data was extracted using the nCounter RCC Collector.

NanoString nCounter miRNA Data Analysis

For platform validation using synthetic oligonucleotides, NanoString nCounter miRNA raw data was normalized for lane-to-lane variation with a dilution series of six spike-in positive controls using nSolver v4.0 software (www.nanostring.com/products/nSolver). The sum of the six positive controls for a given lane were divided by the average sum across lanes to yield a normalization factor, which was then multiplied by the raw counts in each lane to obtain normalized values. For each sample, the mean plus two times the standard deviation of the eight negative controls were subtracted from each miRNA count in that sample. Only miRNAs with non-negative counts across all samples were retained for downstream analysis. The relative miRNA levels were indicated as median fold changes and a cutoff of two fold-change (up or down) was used²⁴. A Venn diagram was prepared using FunRich 3.1.3 open source software^25,26.

Biological Processes and Gene Network Visualization by MetaCore

Biological pathway interactions of microRNA expressions were analyzed using MetaCore pathway analysis of differentially expressed genes (Thomson Reuters, New York, NY)^2,16,27 with p < 0.05 and greater than two-fold change. We performed multiple comparative analysis and enrichment analysis on all five stages of liver disease. Functional gene networks were built based on differentially regulated miRNA gene lists as input to generate disease biomarkers and Gene Ontology terms (Data analyzed by Gene Arrays, Entity of Vedic Research, Inc., New York)^2,16,27.

Statistical Analysis

Paired student’s t test was used to compare diease stage vs healthy samples, with an FDR < 0.05 considered statistically significant and log₂-fold change greater than one. Furthermore, the Benjamini and Hochberg multiple testing adjustment method was applied for all small RNA sequencing studies and an p-value < 0.05 with fold change greater than two for pathway analysis.

Ethics

Data presented in the study was downloaded from the NIH data sets (BioProjects: PRJNA266511 and PRJEB11462). We haven’t recruited any human subjects in this study (Not applicable).

Results

Differential Expression of miRNA in Cirrhosis, LGDN, HGDN, eHCC, and HCC Tissue Samples

We first annotated the datasets to microRNA analysis. Using stringent statistics (FDR < 0.05) with filters set at a log₂-fold change greater than one and total minimum reads > 500, expression data was visualized (Fig. 1A–E, Tables 1–5). Our analysis found 87 miRNAs differentially expressed in cirrhosis compared to normal liver tissue (15 upregulated and 72 downregulated; Fig. 1A, Table 1), 106 miRNAs in LGDN (46 upregulated and 60 downregulated; Fig. 1B, Table 2), 59 miRNAs in HGDN (18 upregulated and 41 downregulated; Fig. 1C, Table 3), 80 miRNAs in eHCC (12 upregulated and 68 downregulated; Fig. 1D, Table 4) and 133 miRNAs in HCC (64 upregulated and 69 downregulated; Fig. 1E, Table 5). The top five differentially upregulated miRNAs in cirrhosis (Table 1) were: miR-7704 (403-fold), miR-22 (143-fold), miR-101 (113-fold), miR-486 (75-fold), and miR-192 (32-fold). The top five downregulated were: miR-122 (312-fold), Let-7g (204-fold), miR-103a (83-fold), miR-532 (79-fold), and miR-451a (62-fold). The top five differentially upregulated miRNAs in LGDN (Table 2) were: miR-141 (625-fold), miR-101 (208-fold), miR-22 (111-fold), miR-16 (61-fold), and miR-486 (35-fold); whereas, the top five downregulated were: miR-451a (513-fold), miR-378c (104-fold), miR-361 (95-fold), miR-122 (81-fold), and miR-30c (78-fold). The top five differentially upregulated miRNAs in HGDN (Table 3) were: miR-101 (266-fold), miR-22 (170-fold), miR-16 (54-fold), miR-192 (45-fold), and miR-19b (34-fold). The top five downregulated were: miR-26b (1 million-fold), miR-20a (1 million-fold), Let-7f (1 million-fold), miR-22–3p (1 million-fold), and Let-7c (364-fold). The top five differentially upregulated miRNAs in eHCC (Table 4) were: miR-101 (215-fold), miR-22 (94-fold), miR-10b (34-fold), miR-19b (34-fold), and miR-192 (29-fold). The top five downregulated were: miR-20a (1 million-fold), miR-22–3p (1 million-fold), miR-26b (1 million-fold), Let-7f (1 million-fold), and miR-30c (3545-fold). The top five differentially upregulated miRNAs in HCC (Table 5) were: miR-142 (1 million-fold), miR-7704 (257-fold), miR-101 (147-fold), miR-23a (124-fold), and miR-22 (85-fold); whereas, the top five downregulated were: miR-122 (513-fold), Let-7g (358-fold), miR-378c (187-fold), miR-185 (68-fold), and miR-451a (58-fold).

Differential expression of miRNAs in liver tissue samples: Differentially expressed miRNAs were quantified (*FDR* < *0.05*) and a heatmap was prepared for each disease stage (Cirrhosis, Low-grade dysplastic nodule, High-grade dysplastic nodule, Early stage Hepatocellular carcinoma, and Advanced stage Hepatocellular carcinoma) with healthy control samples (A–E). Enriched miRNAs for all stages of liver disease were summarized by a Venn diagram, which identified 37 miRNAs commonly expressed in all stages and 29 additional differentially expressed miRNAs were enriched in advanced hepatocellular carcinoma alone (F). (G) A Circos plot was prepared incorporating all differential expressions of miRNAs in cirrhosis, low-grade dysplastic nodule, high-grade dysplastic nodule, early hepatocellular carcinoma, and hepatocellular carcinoma tissue samples compared with healthy samples (FDR < 0.05). Chromosomes and bands were listed in the chromosomal positions of miRNAs affected expression in liver disease vs healthy samples. The innermost ring is for cirrhosis, followed by low-grade dysplastic nodule, high-grade dysplastic nodule, early hepatocellular carcinoma, and hepatocellular carcinoma. Darker and lighter background colors represent upregulated and downregulated genes respectively. We validated the miRNA sequence data using NanoString global miRNA expression assay. Data was exported using nSolver software. (H) A Venn diagram showing miRNA overlap between HCC miRNA-seq data and HCC-NanoString validation data. (I) A heat map illustrating the top 20 up- and down- regulated miRNAs in the HCC-NanoString validation data.

Table 1.

Differentially expressed miRNAs in cirrhosis vs healthy patient’s tissue samples (FDR < 0.05).

microRNA ID	Chromosome	Fold change	FDR
hsa-miR-122-5p	18	−312.73	1.58E-08
hsa-let-7g-5p	3	−204.40	2.12E-04
hsa-mir-103a-2	20	−83.22	3.85E-04
hsa-miR-532-5p	X	−79.93	2.96E-04
hsa-miR-451a	17	−62.96	3.56E-04
hsa-miR-378c	10	−59.31	2.52E-04
hsa-mir-27b	9	−44.44	5.86E-04
hsa-miR-152-3p	17	−44.35	6.26E-04
hsa-mir-194-2	11	−44.16	3.85E-04
hsa-miR-185-5p	22	−39.71	1.44E-03
hsa-miR-128-3p	2	−31.89	2.15E-03
hsa-miR-24-3p	19	−27.07	1.38E-03
hsa-let-7a-5p	11	−25.41	1.22E-04
hsa-let-7b-5p	22	−23.18	6.26E-04
hsa-miR-148b-3p	12	−21.63	9.32E-04
hsa-miR-210-3p	11	−19.22	1.11E-04
hsa-mir-23a	19	−14.26	5.34E-03
hsa-miR-139-5p	11	−14.07	4.82E-03
hsa-mir-101-2	9	−13.98	2.96E-04
hsa-mir-17	13	−13.52	6.00E-03
hsa-miR-99a-5p	21	−12.34	1.77E-04
hsa-miR-93-5p	7	−12.26	6.12E-03
hsa-mir-199a-2	1	−12.07	3.85E-04
hsa-miR-125b-5p	11	−12.00	4.74E-03
hsa-mir-3591	18	−11.52	2.12E-04
hsa-miR-148a-3p	7	−10.94	2.52E-04
hsa-mir-224	X	−10.83	7.73E-03
hsa-mir-23b	9	−10.81	7.29E-03
hsa-mir-3607	5	−9.29	3.71E-04
hsa-miR-450a-5p	X	−7.90	1.22E-02
hsa-miR-200a-3p	1	−7.80	1.08E-02
hsa-mir-140	16	−7.77	1.38E-03
hsa-miR-92a-3p	13	−7.70	1.08E-02
hsa-mir-103a-1	5	−7.57	1.03E-03
hsa-mir-152	17	−7.05	1.49E-02
hsa-mir-378a	5	−6.78	2.78E-02
hsa-miR-126-3p	9	−6.45	1.72E-03
hsa-miR-574-3p	4	−6.41	9.98E-03
hsa-mir-126	9	−6.26	1.55E-02
hsa-mir-128-1	2	−5.62	2.27E-02
hsa-mir-144	17	−5.51	9.16E-03
hsa-miR-29a-3p	7	−5.21	5.08E-03
hsa-mir-21	17	−4.99	3.56E-03
hsa-mir-101-1	1	−4.51	3.95E-03
hsa-let-7e-5p	19	−4.45	2.27E-02
hsa-miR-340-5p	5	−4.04	9.41E-03
hsa-miR-27a-3p	19	−3.92	6.00E-03
hsa-miR-100-5p	11	−3.89	7.36E-03
hsa-miR-26a-5p	12	−3.79	5.34E-03
hsa-mir-199a-1	19	−3.20	8.12E-03
hsa-miR-215-5p	1	−3.07	4.17E-02
hsa-miR-423-3p	17	−3.07	1.60E-02
hsa-miR-21-5p	17	−3.01	1.03E-02
hsa-miR-30b-5p	8	−3.00	2.58E-02
hsa-mir-106b	7	−3.00	1.92E-02
hsa-mir-125b-2	21	−2.96	1.95E-02
hsa-mir-455	9	−2.92	3.76E-02
hsa-mir-195	17	−2.80	3.58E-02
hsa-mir-26b	2	−2.69	1.28E-02
hsa-miR-107	10	−2.62	1.55E-02
hsa-mir-3653	22	−2.58	4.32E-02
hsa-miR-103a-3p	20	−2.40	1.84E-02
hsa-miR-103b	20	−2.40	1.84E-02
hsa-mir-660	X	−2.34	3.88E-02
hsa-let-7a-1	9	−2.21	3.76E-02
hsa-mir-505	X	−2.21	4.32E-02
hsa-mir-192	11	−2.03	2.27E-02
hsa-miR-194-5p	1	−1.86	2.04E-02
hsa-miR-25-3p	7	−1.84	3.23E-02
hsa-let-7i	12	−1.65	4.73E-02
hsa-let-7i-5p	12	−1.58	4.77E-02
hsa-mir-148a	7	−1.48	2.51E-02
hsa-mir-409	14	7.84	4.00E-02
hsa-miR-769-5p	19	8.13	6.63E-03
hsa-miR-320b	1	14.14	2.89E-04
hsa-mir-136	14	15.82	1.80E-02
hsa-miR-127-3p	14	17.15	3.85E-04
hsa-miR-320a	8	17.51	9.02E-06
hsa-mir-186	1	19.52	3.85E-04
hsa-mir-181c	19	24.73	4.46E-02
hsa-miR-1307-5p	10	26.74	6.00E-03
hsa-mir-10b	2	28.57	3.03E-02
hsa-miR-192-5p	11	31.98	1.83E-02
hsa-mir-486-2	8	75.42	9.02E-06
hsa-miR-101-3p	1	113.21	2.51E-02
hsa-mir-22	17	142.96	1.05E-07
hsa-miR-7704	2	403.15	1.11E-04

microRNA ID	Chromosome	Fold change	FDR
hsa-miR-142-5p	17	1000000.00	2.06E-11
hsa-miR-7704	2	256.97	8.73E-05
hsa-miR-101-3p	1	147.24	6.28E-08
hsa-miR-23a-3p	19	123.92	3.72E-08
hsa-mir-22	17	85.32	5.45E-17
hsa-mir-10b	2	73.25	2.02E-10
hsa-miR-130b-3p	22	64.54	1.41E-06
hsa-mir-182	7	61.30	1.51E-02
hsa-mir-16-1	13	57.49	2.69E-07
hsa-miR-197-3p	1	40.60	7.72E-07
hsa-miR-192-5p	11	30.83	1.59E-10
hsa-miR-15a-5p	13	28.71	3.39E-05
hsa-mir-19b-2	X	28.71	6.50E-06
hsa-mir-486-2	8	26.10	2.41E-08
hsa-mir-150	19	23.61	2.20E-03
hsa-mir-98	X	22.41	2.99E-02
hsa-miR-199a-3p	1	21.84	3.26E-04
hsa-mir-181c	19	20.83	2.27E-06
hsa-mir-183	7	19.92	1.02E-03
hsa-mir-181a-1	1	17.61	3.21E-05
hsa-miR-182-5p	7	17.27	1.32E-03
hsa-miR-23b-3p	9	15.46	8.41E-06
hsa-mir-136	14	15.45	8.72E-06
hsa-mir-186	1	15.42	3.23E-10
hsa-mir-130a	11	14.61	1.33E-03
hsa-miR-1307-5p	10	14.53	4.71E-03
hsa-miR-10b-5p	2	13.00	7.50E-07
hsa-let-7f-1	9	12.70	5.27E-05
hsa-mir-92a-1	13	10.86	3.79E-04
hsa-mir-193a	17	10.85	3.49E-05
hsa-miR-126-5p	9	10.17	9.18E-03
hsa-mir-191	3	10.03	1.28E-04
hsa-mir-26a-1	3	8.35	3.16E-03
hsa-mir-181b-1	1	8.16	3.33E-04
hsa-miR-30a-5p	6	8.04	3.05E-04
hsa-mir-30b	8	7.93	4.25E-03
hsa-mir-10a	17	7.78	1.28E-03
hsa-mir-29b-2	1	7.10	1.55E-02
hsa-miR-204-5p	9	6.73	1.89E-03
hsa-mir-93	7	6.48	1.29E-03
hsa-mir-26a-2	12	6.36	1.10E-02
hsa-mir-92a-2	X	6.11	2.72E-03
hsa-miR-127-3p	14	6.02	6.97E-05
hsa-mir-16-2	3	6.00	9.69E-03
hsa-mir-19a	13	5.72	4.58E-03
hsa-miR-29c-3p	1	5.45	1.02E-03
hsa-mir-340	5	5.24	4.02E-03
hsa-mir-145	5	5.22	2.99E-02
hsa-mir-532	X	5.15	1.77E-03
hsa-mir-15b	3	5.13	3.17E-02
hsa-mir-155	21	5.10	4.11E-03
hsa-mir-193b	16	4.87	1.51E-05
hsa-miR-320a	8	4.43	2.20E-03
hsa-miR-484	16	4.20	1.95E-02
hsa-mir-24-1	9	4.11	3.43E-02
hsa-mir-29c	1	3.99	3.36E-02
hsa-mir-365b	17	3.90	1.94E-02
hsa-miR-27b-3p	9	3.76	3.10E-02
hsa-mir-34a	1	3.22	1.32E-03
hsa-miR-769-5p	19	2.90	3.59E-02
hsa-mir-100	11	2.79	4.71E-03
hsa-mir-125b-1	11	2.68	1.72E-02
hsa-miR-221-3p	X	2.68	1.72E-02
hsa-mir-409	14	2.33	1.94E-02
hsa-miR-146a-5p	5	−1.92	1.72E-02
hsa-let-7i	12	−1.95	3.26E-02
hsa-let-7i-5p	12	−1.99	1.29E-02
hsa-miR-486-5p	8	−2.02	3.41E-02
hsa-mir-106b	7	−2.04	1.77E-02
hsa-miR-378a-3p	5	−2.17	1.64E-03
hsa-let-7e-5p	19	−2.21	2.28E-02
hsa-miR-429	1	−2.26	1.60E-02
hsa-mir-484	16	−2.27	4.71E-02
hsa-mir-103a-1	5	−2.36	1.72E-02
hsa-mir-140	16	−2.41	6.53E-03
hsa-miR-92a-3p	13	−2.43	2.22E-02
hsa-mir-455	9	−2.46	2.18E-02
hsa-miR-29a-3p	7	−2.50	2.40E-02
hsa-mir-320a	8	−2.69	1.73E-03
hsa-miR-375	2	−2.75	1.34E-02
hsa-mir-505	X	−2.93	1.88E-03
hsa-mir-99a	21	−3.18	1.99E-04
hsa-miR-215-5p	1	−3.25	4.40E-04
hsa-mir-23b	9	−3.28	1.83E-02
hsa-miR-340-5p	5	−3.48	1.93E-03
hsa-miR-148b-3p	12	−3.71	4.08E-03
hsa-mir-152	17	−3.71	6.20E-04
hsa-mir-126	9	−3.78	3.83E-03
hsa-miR-93-5p	7	−3.80	5.19E-04
hsa-mir-125b-2	21	−3.81	4.58E-04
hsa-mir-17	13	−3.86	2.18E-03
hsa-miR-423-3p	17	−3.90	2.13E-04
hsa-mir-23a	19	−4.19	4.31E-02
hsa-mir-101-1	1	−4.25	8.10E-04
hsa-miR-126-3p	9	−4.32	3.55E-04
hsa-mir-3607	5	−4.41	5.43E-04
hsa-mir-3653	22	−4.48	4.14E-06
hsa-miR-29b-3p	1	−4.55	3.10E-02
hsa-mir-185	22	−4.72	8.54E-05
hsa-mir-200b	1	−4.78	1.02E-03
hsa-mir-200a	1	−4.85	3.16E-03
hsa-miR-148a-3p	7	−5.38	3.59E-05
hsa-miR-24-3p	19	−5.67	1.42E-03
hsa-mir-144	17	−5.79	2.76E-03
hsa-mir-223	X	−6.03	1.37E-02
hsa-mir-3591	18	−7.35	1.58E-06
hsa-miR-139-5p	11	−8.35	5.27E-05
hsa-mir-199a-2	1	−8.74	9.79E-03
hsa-miR-100-5p	11	−8.93	3.26E-09
hsa-let-7a-5p	11	−9.03	5.31E-05
hsa-miR-128-3p	2	−9.93	3.52E-05
hsa-miR-365b-3p	17	−10.55	3.70E-03
hsa-mir-378a	5	−11.05	3.72E-08
hsa-miR-374a-5p	X	−12.17	1.28E-03
hsa-mir-194-2	11	−13.00	9.17E-06
hsa-mir-101-2	9	−13.03	5.26E-07
hsa-miR-532-5p	X	−14.56	9.31E-04
hsa-miR-450a-5p	X	−14.85	1.26E-06
hsa-let-7b-5p	22	−15.34	1.49E-04
hsa-miR-365a-3p	16	−16.01	1.16E-03
hsa-miR-152-3p	17	−16.10	5.27E-05
hsa-miR-200a-3p	1	−21.02	5.19E-04
hsa-mir-27b	9	−22.30	9.04E-08
hsa-mir-424	X	−23.09	1.42E-03
hsa-mir-103a-2	20	−23.41	1.78E-03
hsa-miR-210-3p	11	−27.21	3.26E-09
hsa-miR-99a-5p	21	−29.63	4.87E-12
hsa-miR-125b-5p	11	−32.70	3.37E-09
hsa-miR-451a	17	−57.80	2.07E-04
hsa-miR-185-5p	22	−67.83	4.08E-11
hsa-miR-378c	10	−187.61	4.37E-07
hsa-let-7g-5p	3	−358.28	1.34E-09
hsa-miR-122-5p	18	−513.22	1.17E-06

microRNA ID	Chromosome	Fold change	FDR
hsa-miR-141-3p	12	625.50	7.60E-04
hsa-miR-101-3p	1	208.06	7.45E-06
hsa-mir-22	17	111.76	6.50E-10
hsa-mir-16-1	13	60.69	1.53E-05
hsa-mir-486-2	8	34.93	7.48E-06
hsa-miR-192-5p	11	34.41	2.10E-06
hsa-mir-150	19	33.64	2.15E-04
hsa-miR-199a-3p	1	32.48	8.85E-04
hsa-mir-19b-2	X	32.27	4.61E-06
hsa-miR-15a-5p	13	26.71	1.98E-03
hsa-mir-10b	2	26.66	7.48E-06
hsa-mir-181c	19	26.55	7.45E-06
hsa-mir-181a-1	1	23.72	9.13E-06
hsa-mir-130a	11	22.38	4.29E-05
hsa-miR-424-5p	X	21.67	1.24E-04
hsa-let-7f-1	9	20.45	8.44E-05
hsa-mir-186	1	15.49	7.48E-06
hsa-miR-30a-5p	6	15.34	1.37E-03
hsa-miR-23b-3p	9	13.80	7.60E-04
hsa-mir-26a-1	3	11.20	1.99E-03
hsa-miR-1307-5p	10	10.97	4.06E-02
hsa-mir-181b-1	1	10.53	5.98E-05
hsa-mir-92a-1	13	9.89	1.51E-04
hsa-miR-182-5p	7	9.56	2.65E-02
hsa-mir-10a	17	9.26	2.38E-04
hsa-mir-26a-2	12	8.35	8.27E-03
hsa-mir-191	3	8.25	2.67E-03
hsa-mir-92a-2	X	7.75	1.55E-03
hsa-mir-340	5	7.19	2.26E-03
hsa-miR-126-5p	9	6.67	6.16E-03
hsa-miR-29c-3p	1	6.49	9.39E-04
hsa-mir-16-2	3	6.39	3.99E-02
hsa-miR-127-3p	14	6.04	3.77E-03
hsa-mir-19a	13	5.91	2.26E-03
hsa-mir-30b	8	5.51	1.27E-02
hsa-mir-155	21	5.47	1.70E-02
hsa-mir-100	11	5.34	5.61E-04
hsa-miR-10b-5p	2	5.12	4.41E-03
hsa-mir-145	5	4.71	8.60E-03
hsa-let-7d	9	4.66	2.23E-02
hsa-miR-320a	8	4.27	2.86E-03
hsa-mir-181b-2	9	3.70	1.65E-02
hsa-mir-532	X	3.63	4.22E-02
hsa-mir-125b-1	11	3.18	1.70E-02
hsa-mir-34a	1	2.94	4.06E-02
hsa-mir-193b	16	2.45	4.20E-02
hsa-miR-200a-3p	1	−1.78	4.37E-02
hsa-let-7i-5p	12	−1.78	4.66E-02
hsa-miR-215-5p	1	−1.96	3.38E-02
hsa-mir-455	9	−2.03	4.12E-02
hsa-mir-21	17	−2.08	2.65E-02
hsa-let-7e-5p	19	−2.10	3.33E-02
hsa-mir-3120	1	−2.20	3.66E-02
hsa-miR-92a-3p	13	−2.21	1.74E-02
hsa-mir-101-1	1	−2.22	3.72E-02
hsa-mir-99a	21	−2.28	1.74E-02
hsa-mir-103a-1	5	−2.29	2.11E-02
hsa-mir-224	X	−2.34	3.22E-02
hsa-mir-106b	7	−2.34	1.61E-02
hsa-mir-140	16	−3.01	6.10E-03
hsa-mir-320a	8	−3.02	3.79E-03
hsa-mir-23b	9	−3.12	7.86E-03
hsa-mir-144	17	−3.19	4.12E-02
hsa-mir-152	17	−3.28	2.51E-03
hsa-mir-125b-2	21	−3.47	4.41E-03
hsa-miR-340-5p	5	−3.52	2.16E-03
hsa-miR-148a-3p	7	−4.16	3.07E-03
hsa-miR-148b-3p	12	−4.20	6.24E-03
hsa-mir-17	13	−4.21	1.70E-03
hsa-miR-423-3p	17	−4.43	4.41E-03
hsa-mir-3607	5	−4.44	1.60E-03
hsa-miR-93-5p	7	−4.74	7.05E-04
hsa-mir-126	9	−4.75	5.55E-04
hsa-mir-3653	22	−4.81	1.33E-04
hsa-miR-126-3p	9	−4.89	2.43E-04
hsa-mir-23a	19	−5.30	1.44E-03
hsa-miR-24-3p	19	−5.44	2.26E-03
hsa-let-7a-5p	11	−5.53	7.60E-04
hsa-miR-139-5p	11	−5.53	3.98E-04
hsa-mir-3591	18	−6.30	2.41E-04
hsa-mir-199a-2	1	−6.72	1.77E-04
hsa-let-7b-5p	22	−6.81	8.14E-04
hsa-mir-101-2	9	−6.99	2.88E-04
hsa-mir-378a	5	−7.06	5.82E-05
hsa-miR-100-5p	11	−7.71	1.06E-05
hsa-miR-128-3p	2	−8.01	5.61E-04
hsa-mir-194-2	11	−8.52	3.03E-04
hsa-let-7d-5p	9	−10.76	9.51E-03
hsa-miR-450a-5p	X	−12.31	2.38E-05
hsa-miR-210-3p	11	−12.69	1.77E-05
hsa-miR-152-3p	17	−14.35	2.06E-05
hsa-miR-532-5p	X	−15.17	3.77E-03
hsa-mir-424	X	−15.74	1.47E-05
hsa-mir-27b	9	−17.77	7.48E-06
hsa-let-7c-5p	21	−19.23	1.62E-03
hsa-miR-125b-5p	11	−20.94	1.17E-05
hsa-miR-99a-5p	21	−27.01	4.07E-08
hsa-mir-103a-2	20	−28.04	4.82E-06
hsa-miR-185-5p	22	−68.06	2.60E-08
hsa-miR-374a-5p	X	−69.55	4.61E-06
hsa-let-7g-5p	3	−77.05	4.07E-08
hsa-miR-30c-5p	1	−77.77	1.33E-04
hsa-miR-122-5p	18	−80.83	4.82E-06
hsa-miR-361-3p	X	−94.56	3.30E-05
hsa-miR-378c	10	−103.67	5.71E-05
hsa-miR-451a	17	−513.04	2.05E-06

microRNA ID	Chromosome	Fold change	FDR
hsa-miR-101-3p	1	266.25	1.10E-02
hsa-mir-22	17	169.91	1.30E-10
hsa-mir-16-1	13	53.70	5.87E-03
hsa-miR-192-5p	11	45.02	1.43E-04
hsa-mir-19b-2	X	34.12	1.68E-03
hsa-mir-486-2	8	25.83	1.76E-04
hsa-mir-130a	11	24.80	4.06E-02
hsa-mir-186	1	23.55	2.97E-06
hsa-miR-424-5p	X	20.63	1.50E-02
hsa-mir-10b	2	16.15	1.11E-02
hsa-mir-181a-1	1	16.09	4.85E-04
hsa-miR-320a	8	13.48	2.01E-02
hsa-mir-10a	17	8.93	2.30E-02
hsa-mir-191	3	8.80	2.81E-02
hsa-mir-92a-1	13	8.19	1.46E-02
hsa-miR-127-3p	14	4.94	8.02E-03
hsa-mir-193b	16	4.90	1.09E-02
hsa-mir-100	11	4.11	3.72E-03
hsa-mir-125b-2	21	−2.90	4.18E-02
hsa-mir-106b	7	−3.01	4.27E-02
hsa-miR-99b-5p	19	−3.02	2.47E-02
hsa-mir-200b	1	−3.81	2.62E-02
hsa-mir-140	16	−3.91	1.53E-02
hsa-miR-148b-3p	12	−3.99	2.34E-02
hsa-miR-126-3p	9	−4.34	1.67E-02
hsa-mir-3591	18	−4.43	1.09E-02
hsa-miR-100-5p	11	−4.74	1.48E-03
hsa-mir-3607	5	−5.39	1.35E-02
hsa-miR-423-3p	17	−6.19	3.76E-03
hsa-mir-101-2	9	−6.49	1.53E-02
hsa-miR-93-5p	7	−6.63	2.12E-03
hsa-let-7a-5p	11	−6.99	1.31E-02
hsa-miR-24-3p	19	−7.33	5.92E-03
hsa-mir-199a-2	1	−7.90	1.40E-03
hsa-miR-450a-5p	X	−10.52	3.21E-02
hsa-miR-374a-5p	X	−13.20	1.31E-02
hsa-miR-99a-5p	21	−13.46	2.70E-05
hsa-mir-27b	9	−14.75	4.93E-04
hsa-miR-152-3p	17	−14.77	1.82E-02
hsa-miR-125b-5p	11	−15.62	6.66E-03
hsa-miR-128-3p	2	−16.39	2.13E-02
hsa-miR-210-3p	11	−16.54	1.43E-04
hsa-mir-424	X	−21.44	1.78E-02
hsa-let-7b-5p	22	−21.90	1.81E-02
hsa-miR-200a-3p	1	−24.56	1.34E-02
hsa-miR-532-5p	X	−27.50	1.64E-04
hsa-mir-103a-2	20	−30.41	1.35E-02
hsa-miR-451a	17	−35.59	1.48E-03
hsa-let-7d-5p	9	−35.82	5.12E-03
hsa-miR-185-5p	22	−70.25	3.66E-07
hsa-miR-378c	10	−76.83	2.87E-05
hsa-let-7g-5p	3	−237.19	1.48E-03
hsa-miR-122-5p	18	−243.58	4.71E-07
hsa-miR-30c-5p	1	−298.01	1.10E-04
hsa-let-7c-5p	21	−364.58	3.61E-05
hsa-miR-22-3p	17	−1000000.00	1.03E-16
hsa-let-7f-5p	9	−1000000.00	1.03E-16
hsa-miR-26b-5p	2	−1000000.00	1.95E-16
hsa-miR-20a-5p	13	−1000000.00	3.67E-16

microRNA ID	Chromosome	Fold change	FDR
hsa-miR-101-3p	1	215.60	4.49E-03
hsa-mir-22	17	94.20	9.45E-09
hsa-mir-10b	2	34.24	9.28E-04
hsa-mir-19b-2	X	29.45	9.73E-03
hsa-miR-192-5p	11	29.09	1.14E-03
hsa-mir-486-2	8	26.76	7.29E-04
hsa-miR-320a	8	18.04	9.73E-03
hsa-mir-186	1	16.42	6.95E-05
hsa-miR-127-3p	14	15.94	1.09E-02
hsa-mir-181a-1	1	9.96	2.97E-03
hsa-mir-193b	16	3.63	1.84E-02
hsa-mir-100	11	3.29	1.06E-02
hsa-mir-21	17	−2.07	3.11E-02
hsa-miR-92a-3p	13	−2.20	1.53E-02
hsa-let-7i-5p	12	−2.39	1.84E-02
hsa-miR-99b-5p	19	−2.48	1.84E-02
hsa-mir-455	9	−2.60	2.48E-02
hsa-mir-99a	21	−2.70	1.60E-02
hsa-mir-200b	1	−2.76	2.49E-02
hsa-mir-3653	22	−2.77	1.72E-02
hsa-let-7i	12	−2.78	1.84E-02
hsa-mir-200a	1	−2.80	3.77E-02
hsa-miR-29a-3p	7	−2.87	1.84E-02
hsa-miR-215-5p	1	−2.89	1.77E-02
hsa-mir-101-1	1	−2.97	1.63E-02
hsa-let-7e-5p	19	−3.05	1.59E-02
hsa-miR-27a-3p	19	−3.47	1.44E-02
hsa-mir-106b	7	−3.60	7.83E-03
hsa-mir-128-1	2	−3.63	2.07E-02
hsa-miR-340-5p	5	−3.87	8.94E-03
hsa-miR-150-5p	19	−3.90	1.06E-02
hsa-mir-199a-1	19	−4.02	9.64E-03
hsa-miR-148b-3p	12	−4.14	5.46E-03
hsa-mir-23b	9	−4.38	9.73E-03
hsa-miR-148a-3p	7	−4.55	8.26E-03
hsa-mir-125b-2	21	−4.84	5.35E-03
hsa-mir-103a-1	5	−5.16	5.75E-03
hsa-mir-17	13	−5.22	6.28E-03
hsa-mir-152	17	−5.92	2.77E-03
hsa-mir-3607	5	−6.14	3.00E-03
hsa-miR-100-5p	11	−6.19	4.14E-04
hsa-mir-126	9	−7.00	2.19E-03
hsa-let-7a-5p	11	−7.06	2.77E-03
hsa-mir-140	16	−7.07	2.31E-03
hsa-miR-126-3p	9	−7.18	1.73E-03
hsa-mir-23a	19	−8.07	1.47E-03
hsa-miR-93-5p	7	−8.58	8.01E-04
hsa-mir-3591	18	−8.87	7.27E-04
hsa-mir-101-2	9	−9.79	2.08E-03
hsa-miR-450a-5p	X	−10.96	7.29E-04
hsa-miR-24-3p	19	−11.91	2.08E-03
hsa-mir-144	17	−12.34	4.51E-03
hsa-mir-194-2	11	−12.62	1.84E-03
hsa-miR-200a-3p	1	−12.71	1.39E-02
hsa-miR-139-5p	11	−13.55	1.18E-02
hsa-miR-210-3p	11	−13.69	8.98E-05
hsa-mir-199a-2	1	−14.20	3.57E-04
hsa-miR-128-3p	2	−18.16	7.74E-03
hsa-miR-152-3p	17	−18.61	3.51E-03
hsa-miR-374a-5p	X	−19.82	1.14E-03
hsa-miR-99a-5p	21	−20.45	5.10E-06
hsa-let-7b-5p	22	−21.06	9.64E-03
hsa-miR-125b-5p	11	−24.27	1.78E-04
hsa-miR-532-5p	X	−27.40	5.35E-03
hsa-let-7d-5p	9	−32.21	3.51E-03
hsa-mir-27b	9	−32.67	1.05E-04
hsa-mir-424	X	−46.39	3.61E-03
hsa-mir-103a-2	20	−51.50	4.95E-06
hsa-miR-185-5p	22	−58.42	4.53E-06
hsa-let-7c-5p	21	−68.82	2.19E-03
hsa-miR-378c	10	−82.90	6.70E-07
hsa-miR-451a	17	−188.05	4.57E-04
hsa-miR-122-5p	18	−236.49	5.10E-06
hsa-let-7g-5p	3	−405.25	9.45E-09
hsa-miR-361-3p	X	−2902.32	6.70E-07
hsa-miR-30c-5p	1	−3544.83	2.77E-06
hsa-let-7f-5p	9	−1000000.00	5.42E-17
hsa-miR-22-3p	17	−1000000.00	5.42E-17
hsa-miR-26b-5p	2	−1000000.00	3.58E-16
hsa-miR-20a-5p	13	−1000000.00	4.76E-16

HCC miRNA-seq		HCC Nanostring data-2FC
microRNA ID	Fold change	miRNA	Fold Change
hsa-miR-130b-3p	64.54	hsa-miR-130b-3p	30.06
hsa-miR-182-5p	17.27	hsa-miR-182-5p	3.97
hsa-miR-10b-5p	13.00	hsa-miR-10b-5p	4.08
hsa-miR-320a	4.43	hsa-miR-320a	8.68
hsa-miR-769-5p	2.90	hsa-miR-769-5p	2.91
hsa-miR-375	−2.75	hsa-miR-375	−4.54
hsa-miR-148a-3p	−5.38	hsa-miR-148a-3p	−2.28
hsa-miR-139-5p	−8.35	hsa-miR-139-5p	−6.01
hsa-miR-200a-3p	−21.02	hsa-miR-200a-3p	−5.43
hsa-miR-451a	−57.80	hsa-miR-451a	−3.49
hsa-miR-122-5p	−513.22	hsa-miR-122-5p	−3.31

Feature ID	Chromosome	Fold change	FDR
piR-hsa-28488	6	1966.20	2.53E-07
piR-hsa-7239	2	1629.10	1.08E-06
piR-hsa-5939	12	718.32	1.08E-06
piR-hsa-1338	11	55.63	4.90E-05
piR-hsa-23786	20	18.06	7.48E-05
piR-hsa-3178	20	12.31	1.78E-03
piR-hsa-1823	2	8.23	2.73E-03
piR-hsa-27616	19	5.29	9.09E-03
piR-hsa-14647	9	4.66	8.69E-03
piR-hsa-793	Y	−1.62	4.58E-02
piR-hsa-11362	21	−1.94	2.81E-02
piR-hsa-26686	M	−2.15	2.02E-02
piR-hsa-26685	M	−2.43	1.24E-02
piR-hsa-993	5	−2.46	1.95E-02
piR-hsa-11361	9	−2.53	8.71E-03
piR-hsa-9010	17	−2.95	8.69E-03
piR-hsa-23317	6	−3.13	1.65E-02
piR-hsa-26039	17	−3.58	4.48E-03
piR-hsa-11360	9	−3.70	6.03E-03
piR-hsa-26508.6	X	−4.56	6.03E-03
piR-hsa-24672.1	1	−4.59	2.73E-03
piR-hsa-24672	1	−4.60	2.83E-03
piR-hsa-27282	14	−4.69	9.52E-04
piR-hsa-24672.3	6	−4.71	2.73E-03
piR-hsa-28131.3	3	−4.74	2.33E-02
piR-hsa-1207.2	16	−4.76	2.33E-02
piR-hsa-1207.1	16	−4.78	2.33E-02
piR-hsa-28131.1	1	−4.79	2.33E-02
piR-hsa-1207.3	16	−4.79	2.26E-02
piR-hsa-24672.4	6	−4.80	2.67E-03
piR-hsa-28131	1	−4.84	2.23E-02
piR-hsa-2117	7	−4.85	1.28E-03
piR-hsa-28131.4	6	−4.87	2.26E-02
piR-hsa-1207.4	2	−4.87	2.26E-02
piR-hsa-1207.5	5	−4.87	2.21E-02
piR-hsa-1207	1	−4.88	2.26E-02
piR-hsa-28131.2	16	−4.90	2.24E-02
piR-hsa-26684	M	−4.99	1.89E-03
piR-hsa-26681	M	−4.99	1.89E-03
piR-hsa-27493	1	−5.54	6.01E-03
piR-hsa-2153	11	−5.95	2.47E-02
piR-hsa-25780.10	4	−8.01	1.83E-02
piR-hsa-1177	19	−9.36	1.92E-04
piR-hsa-28478	2	−10.27	3.44E-05
piR-hsa-3200	16	−13.35	7.06E-04
piR-hsa-20757.2	1	−13.91	6.03E-03
piR-hsa-963	17	−16.72	6.03E-03
piR-hsa-20613	7	−20.96	3.11E-03
piR-hsa-25780.9	3	−24.55	1.08E-02
piR-hsa-25780	1	−24.99	1.14E-02
piR-hsa-25780.1	1	−26.09	8.69E-03
piR-hsa-28525	4	−81.22	1.51E-03
piR-hsa-820	2	−99.09	4.65E-04
piR-hsa-5938	3	−108.31	2.58E-06
piR-hsa-5937	3	−120.72	2.53E-07
piR-hsa-952	22	−382.71	1.07E-09

Feature ID	Chromosome	Fold change	FDR
piR-hsa-32299	1	7658.01	3.35E-08
piR-hsa-28488	6	2105.61	5.75E-13
piR-hsa-7239	2	1496.87	8.21E-12
piR-hsa-5939	12	535.89	6.35E-11
piR-hsa-5067.1	3	106.36	3.35E-08
piR-hsa-5067.4	6	101.29	2.01E-05
piR-hsa-1338	11	59.72	5.59E-10
piR-hsa-26754	5	27.08	1.68E-05
piR-hsa-23786	20	24.42	5.04E-05
piR-hsa-28487	2	16.72	4.06E-05
piR-hsa-3178	20	14.72	3.97E-06
piR-hsa-1823	2	10.13	4.39E-04
piR-hsa-14647	9	5.50	1.90E-02
piR-hsa-27616	19	4.59	1.11E-03
piR-hsa-28319	9	2.84	2.34E-02
piR-hsa-28319.1	9	2.75	4.02E-02
piR-hsa-27283	20	−1.61	4.30E-02
piR-hsa-28875	2	−1.76	3.05E-02
piR-hsa-28875.1	M	−1.81	2.88E-02
piR-hsa-17444	20	−2.00	1.13E-02
piR-hsa-1191	17	−2.00	1.81E-02
piR-hsa-993	5	−2.05	2.57E-02
piR-hsa-11362	21	−2.22	1.14E-02
piR-hsa-20266	5	−2.43	2.20E-02
piR-hsa-20266.1	M	−2.47	1.80E-02
piR-hsa-29218	7	−2.49	2.58E-02
piR-hsa-26039	17	−2.56	1.06E-02
piR-hsa-24672	1	−2.88	8.53E-03
piR-hsa-24672.3	6	−2.89	9.35E-03
piR-hsa-24672.4	6	−2.92	8.53E-03
piR-hsa-24672.1	1	−2.94	8.53E-03
piR-hsa-26686	M	−3.29	4.19E-03
piR-hsa-1207.3	16	−3.73	1.14E-02
piR-hsa-28131.3	3	−3.76	1.29E-02
piR-hsa-28131.1	1	−3.76	1.14E-02
piR-hsa-1207.1	16	−3.76	1.14E-02
piR-hsa-28131	1	−3.76	1.29E-02
piR-hsa-1207.2	16	−3.76	1.15E-02
piR-hsa-28131.2	16	−3.79	1.17E-02
piR-hsa-1207.4	2	−3.80	1.14E-02
piR-hsa-1207	1	−3.81	1.15E-02
piR-hsa-1207.5	5	−3.82	1.14E-02
piR-hsa-28131.4	6	−3.86	1.14E-02
piR-hsa-28877	5	−4.01	1.65E-02
piR-hsa-25447	18	−4.34	1.61E-02
piR-hsa-26685	M	−4.57	1.13E-03
piR-hsa-2117	7	−4.72	5.57E-05
piR-hsa-793	Y	−6.89	1.09E-04
piR-hsa-23317	6	−7.42	5.59E-04
piR-hsa-26681	M	−7.51	2.61E-05
piR-hsa-26684	M	−7.51	2.61E-05
piR-hsa-25780.10	4	−8.41	8.46E-03
piR-hsa-27282	14	−9.65	3.76E-07
piR-hsa-28478	2	−9.94	7.01E-07
piR-hsa-12789	Y	−10.01	1.38E-05
piR-hsa-20757.2	1	−10.06	9.74E-03
piR-hsa-2153	11	−10.23	2.96E-03
piR-hsa-27731	7	−10.91	5.62E-03
piR-hsa-27731.1	M	−11.09	4.53E-03
piR-hsa-11360	9	−11.75	1.20E-04
piR-hsa-20613	7	−12.07	8.94E-06
piR-hsa-9010	17	−12.43	3.80E-06
piR-hsa-26508.6	X	−12.64	2.39E-03
piR-hsa-11361	9	−12.75	1.29E-04
piR-hsa-3200	16	−12.86	1.95E-03
piR-hsa-27493	1	−14.50	2.96E-03
piR-hsa-1177	19	−18.54	3.42E-08
piR-hsa-963	17	−20.24	9.10E-04
piR-hsa-25780.1	1	−47.39	1.05E-03
piR-hsa-25780	1	−47.84	1.47E-03
piR-hsa-25780.9	3	−48.83	1.06E-03
piR-hsa-5937	3	−64.99	3.60E-07
piR-hsa-5938	3	−86.53	6.29E-07
piR-hsa-28525	4	−139.56	6.96E-05
piR-hsa-952	22	−424.84	1.07E-05

Feature ID	Chromosome	Fold change	FDR
piR-hsa-32299	1	5556.66	6.74E-06
piR-hsa-28488	6	1804.05	1.10E-09
piR-hsa-7239	2	1138.69	7.04E-09
piR-hsa-5939	12	626.82	1.10E-09
piR-hsa-23655	5	100.84	8.37E-06
piR-hsa-12488	11	31.18	8.05E-06
piR-hsa-6147	2	29.33	1.29E-03
piR-hsa-12488.1	M	27.82	8.56E-06
piR-hsa-1338	11	17.68	2.04E-08
piR-hsa-23786	20	13.72	1.96E-07
piR-hsa-26131	7	10.87	2.05E-02
piR-hsa-15023.1	M	7.25	2.11E-02
piR-hsa-15023	8	6.80	3.64E-02
piR-hsa-28190	11	6.77	8.81E-04
piR-hsa-3178	20	6.45	4.65E-03
piR-hsa-25783.4	16	5.91	4.11E-03
piR-hsa-27616	19	5.75	2.05E-04
piR-hsa-25783.8	6	5.71	4.65E-03
piR-hsa-25783.1	16	5.63	5.28E-03
piR-hsa-25783.6	2	5.51	5.08E-03
piR-hsa-25783	1	5.44	5.63E-03
piR-hsa-25783.2	16	5.37	4.65E-03
piR-hsa-25783.7	5	5.16	4.11E-03
piR-hsa-25783.3	16	5.09	5.63E-03
piR-hsa-25783.5	17	5.08	6.42E-03
piR-hsa-28390	2	4.23	9.37E-03
piR-hsa-28390.1	8	3.89	2.11E-02
piR-hsa-1823	2	3.07	2.27E-03
piR-hsa-1834	17	−1.77	3.29E-02
piR-hsa-12789	Y	−1.94	2.96E-02
piR-hsa-26685	M	−2.07	3.47E-02
piR-hsa-25447	18	−2.31	4.40E-03
piR-hsa-793	Y	−2.31	1.08E-02
piR-hsa-11361	9	−2.71	1.13E-02
piR-hsa-993	5	−2.72	1.46E-03
piR-hsa-11360	9	−3.13	4.77E-03
piR-hsa-26508.6	X	−3.52	6.43E-03
piR-hsa-26039	17	−3.58	4.56E-04
piR-hsa-9010	17	−3.85	9.29E-04
piR-hsa-27493	1	−4.12	1.06E-02
piR-hsa-26681	M	−4.44	2.95E-04
piR-hsa-26684	M	−4.44	2.95E-04
piR-hsa-2153	11	−4.59	1.34E-02
piR-hsa-27282	14	−5.30	2.67E-05
piR-hsa-17444	20	−6.07	3.45E-06
piR-hsa-3200	16	−6.86	3.79E-05
piR-hsa-1177	19	−7.31	5.33E-05
piR-hsa-2117	7	−7.41	1.76E-06
piR-hsa-28478	2	−9.72	3.84E-07
piR-hsa-25780.9	3	−13.66	3.59E-03
piR-hsa-25780.1	1	−14.57	1.48E-03
piR-hsa-25780	1	−14.89	1.71E-03
piR-hsa-963	17	−16.82	2.62E-07
piR-hsa-5938	3	−36.11	7.78E-07
piR-hsa-20613	7	−36.17	1.10E-09
piR-hsa-5937	3	−36.80	1.76E-06
piR-hsa-28525	4	−81.85	1.90E-09
piR-hsa-820	2	−100.92	4.08E-07
piR-hsa-12759	5	−269.75	2.72E-06
piR-hsa-952	22	−449.82	9.17E-11

Feature ID	Chromosome	Fold change	FDR
piR-hsa-28488	6	1013.41	5.02E-06
piR-hsa-7239	2	791.73	9.22E-06
piR-hsa-5939	12	281.36	2.40E-06
piR-hsa-23655	5	96.41	3.64E-04
piR-hsa-6147	2	25.77	2.93E-02
piR-hsa-1338	11	19.90	4.58E-06
piR-hsa-3178	20	9.12	1.10E-04
piR-hsa-27616	19	6.05	1.41E-03
piR-hsa-25783.4	16	4.10	1.33E-02
piR-hsa-1823	2	4.06	2.63E-03
piR-hsa-25783.6	2	3.78	3.36E-02
piR-hsa-25783.5	17	3.46	3.59E-02
piR-hsa-1834	17	−2.00	4.81E-02
piR-hsa-993	5	−2.74	9.03E-03
piR-hsa-26685	M	−2.79	2.16E-02
piR-hsa-23317	6	−2.93	3.62E-02
piR-hsa-26039	17	−2.98	1.02E-02
piR-hsa-11360	9	−3.62	2.78E-02
piR-hsa-27493	1	−4.62	1.22E-02
piR-hsa-17444	20	−4.65	3.76E-04
piR-hsa-12789	Y	−4.82	3.75E-03
piR-hsa-20757.2	1	−5.60	4.06E-02
piR-hsa-9010	17	−6.88	1.47E-04
piR-hsa-26684	M	−7.15	1.13E-04
piR-hsa-26681	M	−7.15	1.13E-04
piR-hsa-3200	16	−7.38	7.87E-04
piR-hsa-27282	14	−8.31	1.56E-06
piR-hsa-2153	11	−8.92	4.32E-02
piR-hsa-2117	7	−11.59	1.03E-05
piR-hsa-1177	19	−12.56	1.64E-05
piR-hsa-28478	2	−15.42	4.78E-07
piR-hsa-25780.9	3	−16.03	3.03E-02
piR-hsa-25780.1	1	−16.41	4.25E-03
piR-hsa-25780	1	−16.85	2.78E-02
piR-hsa-963	17	−20.25	8.80E-03
piR-hsa-20613	7	−39.75	2.27E-07
piR-hsa-5937	3	−44.83	9.22E-06
piR-hsa-5938	3	−45.11	5.46E-05
piR-hsa-25782.4	16	−94.21	7.87E-04
piR-hsa-25782.3	16	−104.58	3.65E-04
piR-hsa-28525	4	−116.32	2.79E-10
piR-hsa-25782.6	2	−126.18	4.15E-04
piR-hsa-820	2	−130.03	3.65E-04
piR-hsa-25782.8	6	−160.04	5.10E-04
piR-hsa-25782.2	16	−165.67	5.83E-05
piR-hsa-25782.1	16	−181.07	5.46E-05
piR-hsa-25782.5	17	−309.27	3.15E-05
piR-hsa-952	22	−469.05	1.02E-04
piR-hsa-12759	5	−533.60	4.46E-05

Feature ID	Chromosome	Fold change	FDR
piR-hsa-32299	1	4044.62	9.95E-10
piR-hsa-23670.1	8	2335.40	4.15E-14
piR-hsa-24684.5	5	2219.85	3.09E-08
piR-hsa-24684	1	2072.08	7.08E-10
piR-hsa-28488	6	1098.53	1.93E-15
piR-hsa-7239	2	949.32	2.37E-14
piR-hsa-24684.1	1	761.46	2.93E-08
piR-hsa-5939	12	529.51	2.33E-15
piR-hsa-24684.2	1	375.35	8.29E-08
piR-hsa-24684.3	11	355.01	1.96E-07
piR-hsa-24684.7	5	331.73	3.48E-06
piR-hsa-24684.8	6	241.61	7.96E-07
piR-hsa-24684.4	5	228.88	2.41E-07
piR-hsa-23655	5	106.32	2.38E-06
piR-hsa-24684.6	5	88.62	4.13E-05
piR-hsa-5067.1	3	46.48	1.07E-08
piR-hsa-5067.4	6	44.68	3.71E-06
piR-hsa-12488	11	39.49	1.55E-06
piR-hsa-12488.1	M	35.19	3.88E-06
piR-hsa-6147	2	30.46	1.03E-03
piR-hsa-26131	7	20.96	5.50E-04
piR-hsa-28378.6	6	19.88	4.16E-08
piR-hsa-28374.6	6	19.88	4.16E-08
piR-hsa-1338	11	19.63	4.37E-09
piR-hsa-28378.2	5	18.44	6.16E-08
piR-hsa-28374.2	5	18.44	6.16E-08
piR-hsa-28378	12	18.44	3.01E-08
piR-hsa-28374	12	18.44	3.01E-08
piR-hsa-28374.4	6	18.29	3.90E-08
piR-hsa-28378.4	6	18.29	3.90E-08
piR-hsa-28374.5	6	17.33	3.85E-08
piR-hsa-28378.5	6	17.33	3.85E-08
piR-hsa-28374.1	12	17.22	4.14E-08
piR-hsa-28378.1	12	17.22	4.14E-08
piR-hsa-23786	20	16.93	4.71E-12
piR-hsa-28374.3	6	16.31	4.23E-08
piR-hsa-28378.3	6	16.31	4.23E-08
piR-hsa-26754	5	14.19	8.68E-05
piR-hsa-3178	20	12.26	8.67E-07
piR-hsa-28487	2	9.95	3.28E-08
piR-hsa-15023.1	M	8.68	8.72E-04
piR-hsa-15023	8	8.24	8.71E-04
piR-hsa-28116.3	6	7.13	2.75E-02
piR-hsa-28116.1	17	7.05	3.12E-02
piR-hsa-28116.2	6	6.84	3.45E-02
piR-hsa-28116.7	6	6.73	3.72E-02
piR-hsa-28116.6	6	6.64	4.50E-02
piR-hsa-28116.4	6	6.48	2.58E-02
piR-hsa-28116.8	6	6.36	2.91E-02
piR-hsa-28116.9	6	6.15	3.63E-02
piR-hsa-28190	11	6.13	6.32E-05
piR-hsa-2155	M	5.29	4.29E-02
piR-hsa-27616	19	4.98	5.27E-07
piR-hsa-7193.2	1	4.61	7.08E-03
piR-hsa-7193.3	15	4.49	1.39E-02
piR-hsa-7193.6	2	4.44	1.48E-02
piR-hsa-7193.5	15	4.42	4.51E-03
piR-hsa-7193.1	1	4.33	7.65E-03
piR-hsa-7193.4	15	4.30	7.43E-03
piR-hsa-23619.1	16	4.23	1.70E-02
piR-hsa-25783.4	16	4.20	1.61E-02
piR-hsa-23619.4	6	4.16	1.18E-02
piR-hsa-7193	1	4.12	1.39E-02
piR-hsa-23619	1	4.09	2.36E-02
piR-hsa-25783.6	2	4.05	2.06E-02
piR-hsa-25783.8	6	4.05	1.58E-02
piR-hsa-23619.3	5	4.04	2.88E-02
piR-hsa-25783.1	16	4.03	1.86E-02
piR-hsa-28390	2	3.98	3.29E-03
piR-hsa-25783	1	3.98	2.15E-02
piR-hsa-14647	9	3.87	2.85E-04
piR-hsa-25783.2	16	3.86	2.52E-02
piR-hsa-23619.2	5	3.82	2.04E-02
piR-hsa-28875	2	3.80	2.40E-02
piR-hsa-28875.1	M	3.79	2.91E-02
piR-hsa-25783.3	16	3.75	2.06E-02
piR-hsa-25783.7	5	3.69	2.91E-02
piR-hsa-25783.5	17	3.64	2.86E-02
piR-hsa-28390.1	8	3.62	4.46E-03
piR-hsa-1823	2	3.38	9.34E-04
piR-hsa-1742	1	2.95	8.96E-05
piR-hsa-28319.1	9	1.85	1.01E-02
piR-hsa-28319	9	1.80	1.14E-02
piR-hsa-28382	12	−1.63	4.36E-02
piR-hsa-26686	M	−1.84	2.03E-02
piR-hsa-11362	21	−1.88	3.47E-02
piR-hsa-9010	17	−1.88	1.48E-02
piR-hsa-993	5	−1.90	9.08E-03
piR-hsa-20266	5	−2.29	2.15E-03
piR-hsa-26685	M	−2.35	2.99E-03
piR-hsa-20266.1	M	−2.38	9.82E-04
piR-hsa-1043	4	−2.40	9.82E-04
piR-hsa-24672.3	6	−2.41	6.97E-03
piR-hsa-24672	1	−2.43	5.81E-03
piR-hsa-24672.4	6	−2.44	7.14E-03
piR-hsa-24672.1	1	−2.45	6.07E-03
piR-hsa-23317	6	−2.65	9.61E-03
piR-hsa-28212.2	7	−2.69	6.82E-04
piR-hsa-28212.1	11	−2.70	6.10E-04
piR-hsa-25447	18	−2.82	9.80E-05
piR-hsa-28212	1	−2.82	2.94E-04
piR-hsa-27282	14	−2.99	1.91E-04
piR-hsa-25780.10	4	−3.11	2.88E-02
piR-hsa-26039	17	−3.30	4.84E-05
piR-hsa-17444	20	−3.46	7.18E-06
piR-hsa-11361	9	−3.66	3.52E-03
piR-hsa-26508.6	X	−3.66	2.50E-03
piR-hsa-2153	11	−4.00	2.00E-03
piR-hsa-20757.2	1	−4.30	3.05E-02
piR-hsa-26681	M	−4.36	1.77E-05
piR-hsa-26684	M	−4.36	1.77E-05
piR-hsa-2117	7	−5.03	7.76E-06
piR-hsa-11360	9	−5.05	1.59E-04
piR-hsa-1177	19	−5.27	2.17E-06
piR-hsa-27493	1	−5.27	7.05E-04
piR-hsa-3200	16	−7.10	7.96E-07
piR-hsa-20613	7	−7.45	9.32E-07
piR-hsa-28478	2	−10.34	4.94E-11
piR-hsa-963	17	−11.58	6.23E-08
piR-hsa-25780.1	1	−11.82	2.13E-04
piR-hsa-25780	1	−11.96	2.34E-04
piR-hsa-25780.9	3	−12.16	3.07E-04
piR-hsa-5936	5	−20.70	3.07E-10
piR-hsa-5937	3	−51.29	3.07E-10
piR-hsa-5938	3	−56.84	4.68E-09
piR-hsa-28525	4	−57.64	4.37E-06
piR-hsa-820	2	−78.24	9.30E-06
piR-hsa-952	22	−517.94	1.14E-19

lncRNA ID	Chromosome	Fold change	FDR
lnc-C21orf67-10:1	21	23661.18	1.25E-09
lnc-CRK-3:2	17	19137.71	4.54E-08
lnc-FBXO11-7:1	2	5354.15	1.25E-09
lnc-GCNT1-4:6	9	382.70	4.77E-08
lnc-GCNT1-4:5	9	320.01	8.81E-07
lnc-GCNT1-4:2	9	284.32	5.92E-05
lnc-GCNT1-4:3	9	284.07	4.24E-05
lnc-GCNT1-4:4	9	278.80	8.29E-05
HAGLR:1	2	259.55	2.06E-06
HAGLR:31	2	259.36	2.06E-06
lnc-ADCY10-1:1	1	199.46	3.12E-06
lnc-UBC-3:1	12	146.21	8.81E-07
lnc-TRIM27-18:1	6	68.97	7.70E-04
lnc-AC106017.1.1-2:1	17	52.61	1.30E-09
lnc-FNBP1L-2:1	1	36.38	3.18E-05
lnc-FCGR3A-3:1	1	30.45	3.64E-08
lnc-ZNF391-5:2	6	26.39	2.34E-07
lnc-AC102948.1.1-4:1	17	25.97	3.76E-07
lnc-ECHDC1-1:1	6	16.78	4.18E-04
lnc-MAP1LC3B-7:1	16	16.24	4.41E-06
lnc-PRRC2C-5:1	1	15.40	5.83E-05
lnc-C6orf100-12:1	6	15.25	9.73E-06
LIMD1-AS1:6	3	14.15	1.96E-05
lnc-GNGT2-1:2	17	14.13	5.72E-04
lnc-GPR39-7:2	2	11.30	1.17E-02
SNHG1:34	11	8.88	5.63E-05
lnc-TMPO-1:1	12	6.71	4.40E-03
lnc-HIST1H2BI-2:2	6	6.70	8.37E-04
lnc-NARF-2:2	17	6.53	7.74E-04
lnc-SAG-4:1	2	6.35	6.94E-03
lnc-TRIM7-2:5	5	5.95	7.95E-03
lnc-PARVG-4:1	22	4.65	1.98E-03
MIR22HG:35	17	4.37	4.94E-02
MIR22HG:18	17	4.37	4.94E-02
MIR22HG:24	17	4.32	4.77E-02
lnc-GRAP-1:1	17	4.27	4.96E-04
lnc-AC007952.2.1-2:1	17	4.26	5.31E-04
MIR22HG:47	17	4.25	4.87E-02
lnc-AC007952.1.1-3:1	17	4.21	4.04E-04
lnc-AC007952.2-2:3	17	4.16	4.51E-04

lncRNA ID	Chromosome	Fold change	FDR
lnc-CRK-3:2	17	6384.96	9.03E-05
lnc-GCNT1-4:6	9	289.82	1.66E-08
lnc-GCNT1-4:5	9	269.34	1.66E-08
HAGLR:1	2	251.27	3.02E-03
lnc-GCNT1-4:2	9	240.21	1.33E-07
lnc-GCNT1-4:3	9	237.82	1.33E-07
lnc-GCNT1-4:4	9	237.45	1.33E-07
lnc-UBC-3:1	12	202.61	4.21E-05
lnc-TRIM27-18:1	6	170.61	4.91E-03
lnc-AC106017.1.1-2:1	17	51.74	2.12E-05
lnc-FNBP1L-2:1	1	24.51	2.18E-03
lnc-GNGT2-1:2	17	23.07	4.17E-04
LINC00273:8	16	20.55	1.80E-02
lnc-AC102948.1.1-4:1	17	15.69	8.11E-05
LIMD1-AS1:6	3	15.67	3.53E-04
lnc-PRRC2C-5:1	1	15.57	1.02E-03
lnc-ZNF391-5:2	6	14.67	1.26E-03
lnc-GPR39-7:2	2	11.36	1.21E-03
lnc-ZNF133-3:1	20	5.79	3.20E-02
lnc-SAG-4:1	2	4.05	1.22E-02
MIR22HG:35	17	2.84	1.32E-02
MIR22HG:18	17	2.84	1.32E-02
MIR22HG:24	17	2.84	1.16E-02
MIR22HG:47	17	2.83	1.19E-02
FTX:29	X	−1.01	4.72E-02
lnc-SLC25A30-3:1	13	−1.61	4.56E-02
LINC-PINT:28	7	−1.66	4.39E-02
lnc-VMP1-3:3	17	−1.70	3.20E-02
LINC-PINT:29	7	−1.74	3.44E-02
lnc-C9orf100-1:1	9	−1.90	3.30E-02
lnc-RPL13A-1:5	19	−1.97	3.73E-02
LINC00472:10	6	−1.98	2.50E-02
lnc-SNURF-1:17	15	−1.99	4.63E-02
SNHG16:42	17	−2.01	2.10E-02
lnc-KIF20B-3:1	10	−2.02	3.04E-02
lnc-ZNF169-7:7	9	−2.07	2.64E-02
MIR193BHG:18	16	−2.12	2.17E-02
lnc-FPR2-1:35	19	−2.27	2.20E-02
LINC00324:3	17	−2.30	1.37E-02
lnc-SNAPC5-4:3	15	−2.35	2.63E-02

lncRNA ID	Chromosome	Fold change	FDR
lnc-GCNT1-4:6	9	306.64	2.76E-08
lnc-GCNT1-4:5	9	305.75	2.69E-08
lnc-GCNT1-4:2	9	302.98	4.40E-08
lnc-GCNT1-4:3	9	301.19	4.40E-08
lnc-GCNT1-4:4	9	295.48	4.40E-08
lnc-UBC-3:1	12	292.71	1.48E-05
lnc-TRIM27-18:1	6	238.48	1.25E-03
LINC00273:8	16	33.66	2.40E-02
lnc-FNBP1L-2:1	1	17.70	1.66E-02
lnc-GNGT2-1:2	17	16.60	6.70E-05
lnc-SDHC-3:1	1	15.91	4.38E-03
lnc-PRRC2C-5:1	1	13.19	3.82E-05
lnc-TRIM7-2:5	5	13.02	1.95E-04
lnc-OR2V2-3:1	5	12.02	2.11E-02
lnc-ZNF391-5:2	6	11.70	7.69E-03
lnc-IL17RB-3:1	3	8.65	2.54E-02
LIMD1-AS1:6	3	7.10	1.81E-03
MIR22HG:47	17	5.12	6.22E-05
MIR22HG:24	17	5.12	6.10E-05
MIR22HG:18	17	5.08	6.47E-05
MIR22HG:35	17	5.08	6.47E-05
lnc-ZNF133-3:1	20	4.65	8.10E-03
lnc-AL669831.1-11:4	1	4.19	2.94E-03
lnc-SAG-4:1	2	3.83	2.18E-03
lnc-RRBP1-3:1	20	−1.51	4.91E-02
lnc-REG3G-6:1	2	−1.75	3.84E-02
lnc-RP4-695O20__B.10.1-3:10	22	−1.93	4.56E-02
lnc-RP4-695O20__B.10.1-3:9	22	−1.93	4.60E-02
lnc-RP4-695O20__B.10.1-3:12	22	−1.93	4.55E-02
lnc-MON2-2:8	12	−1.97	4.43E-02
lnc-MON2-2:10	12	−1.97	4.31E-02
lnc-MON2-2:2	12	−1.98	4.33E-02
lnc-HNRNPA2B1-10:4	7	−2.04	4.08E-02
lnc-IRS4-2:1	X	−2.04	1.37E-02
MIR210HG:7	11	−2.05	3.49E-02
SNHG16:42	17	−2.14	9.50E-03
LINC00273:11	16	−2.24	1.39E-02
lnc-SLC25A30-3:1	13	−2.28	4.56E-02
lnc-NEMF-1:4	14	−2.32	3.84E-02
lnc-FPR2-1:35	19	−2.67	2.60E-02

Feature ID	Chromosome	Fold change	FDR
hsa_circ_0040679	16	2327.99	1.34E-08
hsa_circ_0015774	1	1621.70	5.47E-10
hsa_circ_0016456	1	1039.17	1.35E-07
hsa_circ_0015637	1	809.57	3.13E-11
hsa_circ_0014848	1	591.30	7.64E-07
hsa_circ_0054435	2	451.43	3.58E-08
hsa_circ_0087948	9	180.01	1.31E-14
hsa_circ_0087119	9	122.08	3.40E-04
hsa_circ_0019374	10	97.40	2.73E-06
hsa_circ_0012861	1	86.11	2.10E-06
hsa_circ_0008347	19	59.74	8.62E-05
hsa_circ_0069968	4	38.17	2.86E-06
hsa_circ_0069969	4	38.17	2.83E-06
hsa_circ_0079763	7	27.36	1.85E-02
hsa_circ_0006061	1	27.15	1.32E-08
hsa_circ_0069749	4	11.31	4.43E-04
hsa_circ_0009016	11	10.30	1.30E-06
hsa_circ_0043602	17	5.39	1.25E-02
hsa_circ_0043601	17	5.39	1.28E-02
hsa_circ_0043605	17	5.29	9.64E-03
hsa_circ_0043604	17	5.26	1.01E-02
hsa_circ_0043603	17	5.21	1.42E-02
hsa_circ_0034154	15	2.97	4.16E-02
hsa_circ_0004659	17	1.73	2.23E-02
hsa_circ_0034118	15	−2.15	1.70E-02
hsa_circ_0034110	15	−2.44	1.48E-02
hsa_circ_0055902	2	−2.53	2.75E-03
hsa_circ_0034138	15	−2.67	7.89E-03
hsa_circ_0022568	11	−2.96	4.03E-03
hsa_circ_0000146	1	−2.97	2.14E-02
hsa_circ_0031772	14	−3.14	5.91E-04
hsa_circ_0008733	1	−3.20	6.59E-03
hsa_circ_0002978	1	−3.21	6.16E-03
hsa_circ_0004784	1	−3.22	6.16E-03
hsa_circ_0006643	1	−3.22	5.89E-03
hsa_circ_0090906	X	−3.30	1.99E-02
hsa_circ_0000705	16	−3.55	2.16E-03
hsa_circ_0063778	22	−3.75	2.20E-03
hsa_circ_0067418	3	−4.22	3.72E-04
hsa_circ_0007319	7	−4.88	3.74E-06

Feature ID	Chromosome	Fold change	FDR
hsa_circ_0021905	11	800542.00	5.29E-31
hsa_circ_0016456	1	1204.47	4.52E-10
hsa_circ_0015637	1	607.83	1.37E-18
hsa_circ_0087119	9	602.14	3.06E-09
hsa_circ_0014848	1	437.51	1.49E-09
hsa_circ_0015774	1	308.14	4.00E-11
hsa_circ_0040679	16	228.28	5.92E-12
hsa_circ_0087948	9	125.30	4.13E-16
hsa_circ_0008347	19	114.16	1.65E-14
hsa_circ_0019374	10	61.21	1.36E-04
hsa_circ_0012861	1	24.27	6.41E-11
hsa_circ_0043602	17	21.84	1.24E-05
hsa_circ_0043601	17	21.55	1.23E-05
hsa_circ_0043605	17	21.26	1.63E-06
hsa_circ_0043604	17	21.13	1.68E-06
hsa_circ_0043603	17	21.00	1.37E-05
hsa_circ_0006061	1	13.52	1.62E-09
hsa_circ_0002189	8	7.83	7.01E-07
hsa_circ_0009060	16	7.02	1.68E-05
hsa_circ_0034021	14	5.93	1.57E-02
hsa_circ_0005554	14	5.15	1.94E-02
hsa_circ_0009016	11	4.44	2.22E-07
hsa_circ_0051491	19	3.74	8.30E-05
hsa_circ_0064383	3	3.61	1.36E-04
hsa_circ_0016169	1	2.87	3.30E-02
hsa_circ_0004659	17	1.56	2.21E-02
hsa_circ_0089763	M	−1.12	1.01E-03
hsa_circ_0071319	4	−1.54	2.20E-02
hsa_circ_0010166	1	−1.91	3.06E-02
hsa_circ_0019218	10	−2.20	6.32E-04
hsa_circ_0004489	14	−2.21	3.26E-03
hsa_circ_0034110	15	−2.23	1.15E-02
hsa_circ_0000705	16	−2.38	3.34E-05
hsa_circ_0055902	2	−2.39	8.97E-05
hsa_circ_0001853	9	−2.41	1.96E-03
hsa_circ_0090906	X	−2.47	1.19E-02
hsa_circ_0063778	22	−2.50	6.21E-03
hsa_circ_0022568	11	−2.52	1.42E-03
hsa_circ_0034138	15	−2.54	6.47E-03
hsa_circ_0092280	1	−2.69	1.19E-02
hsa_circ_0002571	14	−2.76	1.58E-03
hsa_circ_0034121	15	−2.97	8.08E-03
hsa_circ_0034117	15	−2.98	1.75E-02
hsa_circ_0092342	11	−2.99	1.47E-03
hsa_circ_0022547	11	−3.30	5.06E-03
hsa_circ_0067418	3	−3.70	3.66E-05
hsa_circ_0040412	16	−3.82	4.65E-05
hsa_circ_0092300	2	−3.82	1.70E-05
hsa_circ_0003812	11	−3.90	1.13E-03
hsa_circ_0004287	11	−4.24	1.59E-07
hsa_circ_0081371	7	−4.36	6.84E-07
hsa_circ_0092275	1	−4.65	2.76E-04
hsa_circ_0052884	2	−4.89	2.41E-06
hsa_circ_0092282	1	−5.04	5.12E-09
hsa_circ_0052882	2	−5.37	1.52E-07
hsa_circ_0034118	15	−6.34	5.39E-04
hsa_circ_0071323	4	−6.56	1.50E-05
hsa_circ_0007319	7	−6.85	1.94E-11
hsa_circ_0007956	18	−7.25	3.56E-06
hsa_circ_0024019	11	−7.44	2.24E-06
hsa_circ_0024018	11	−7.58	1.65E-06
hsa_circ_0071320	4	−7.99	2.41E-06
hsa_circ_0039972	16	−8.42	4.52E-10
hsa_circ_0069967	4	−11.02	4.61E-11
hsa_circ_0043980	17	−11.70	1.15E-05
hsa_circ_0069970	4	−13.17	1.15E-09
hsa_circ_0092360	17	−15.18	2.95E-08
hsa_circ_0076872	6	−97.52	8.42E-19
hsa_circ_0035407	15	−783.68	3.39E-11
hsa_circ_0035409	15	−1219.10	3.39E-11

Feature ID	Chromosome	Fold change	FDR
hsa_circ_0087119	9	454.61	2.78E-05
hsa_circ_0014848	1	454.34	1.95E-05
hsa_circ_0015637	1	368.71	7.33E-11
hsa_circ_0015774	1	126.00	1.72E-08
hsa_circ_0008347	19	116.32	2.00E-09
hsa_circ_0040679	16	111.54	1.93E-09
hsa_circ_0087948	9	60.83	7.33E-11
hsa_circ_0043602	17	19.26	6.33E-04
hsa_circ_0043601	17	19.22	6.33E-04
hsa_circ_0043605	17	18.79	5.24E-04
hsa_circ_0043603	17	18.67	5.99E-04
hsa_circ_0043604	17	18.63	5.37E-04
hsa_circ_0006061	1	10.72	2.54E-06
hsa_circ_0009016	11	5.35	3.47E-04
hsa_circ_0051491	19	4.94	2.45E-03
hsa_circ_0064383	3	2.35	3.79E-02
hsa_circ_0063778	22	−1.73	4.65E-02
hsa_circ_0006940	14	−1.82	4.56E-02
hsa_circ_0031772	14	−1.86	1.94E-02
hsa_circ_0055902	2	−1.97	1.26E-02
hsa_circ_0000705	16	−2.14	4.01E-03
hsa_circ_0004489	14	−2.29	1.54E-02
hsa_circ_0001853	9	−2.30	1.05E-02
hsa_circ_0010166	1	−2.45	3.93E-02
hsa_circ_0034110	15	−2.53	2.13E-02
hsa_circ_0002571	14	−3.01	2.14E-03
hsa_circ_0052884	2	−3.15	4.52E-03
hsa_circ_0040412	16	−3.37	1.25E-03
hsa_circ_0022568	11	−3.37	8.86E-04
hsa_circ_0034117	15	−3.70	3.26E-02
hsa_circ_0034138	15	−3.74	1.60E-03
hsa_circ_0022547	11	−3.85	1.41E-02
hsa_circ_0071320	4	−4.26	1.78E-03
hsa_circ_0092342	11	−4.49	1.37E-03
hsa_circ_0092282	1	−4.70	4.02E-05
hsa_circ_0069967	4	−4.73	6.48E-05
hsa_circ_0092300	2	−4.87	1.46E-04
hsa_circ_0081371	7	−4.92	1.09E-04
hsa_circ_0034118	15	−5.09	1.31E-02
hsa_circ_0092275	1	−5.35	1.93E-03
hsa_circ_0069970	4	−5.44	1.47E-04
hsa_circ_0092280	1	−5.76	4.92E-04
hsa_circ_0034121	15	−6.03	1.35E-02
hsa_circ_0004287	11	−6.07	8.33E-05
hsa_circ_0007319	7	−8.02	1.86E-08
hsa_circ_0043980	17	−8.35	1.31E-03
hsa_circ_0024018	11	−8.97	3.79E-05
hsa_circ_0024019	11	−9.04	3.49E-05
hsa_circ_0039972	16	−9.50	1.79E-05
hsa_circ_0007956	18	−10.74	1.52E-05
hsa_circ_0092360	17	−25.62	1.66E-07
hsa_circ_0076872	6	−71.14	2.26E-10
hsa_circ_0089763	M	−86.14	9.20E-06
hsa_circ_0035407	15	−790.56	6.21E-07
hsa_circ_0035409	15	−2745.28	5.53E-08
hsa_circ_0006257	12	−48722.51	2.34E-09

Feature ID	Chromosome	Fold change	FDR
hsa_circ_0054435	2	2907.43	3.25E-03
hsa_circ_0015637	1	454.29	1.93E-07
hsa_circ_0015774	1	416.69	1.82E-05
hsa_circ_0087119	9	265.25	7.85E-04
hsa_circ_0040679	16	211.05	1.61E-06
hsa_circ_0087948	9	90.25	4.85E-07
hsa_circ_0008347	19	83.53	4.47E-06
hsa_circ_0006061	1	13.47	1.72E-03
hsa_circ_0009016	11	7.07	4.46E-03
hsa_circ_0043602	17	6.37	3.17E-02
hsa_circ_0043601	17	6.36	3.58E-02
hsa_circ_0043605	17	6.16	2.94E-02
hsa_circ_0043603	17	6.16	3.60E-02
hsa_circ_0051491	19	3.45	1.84E-02
hsa_circ_0063778	22	−1.93	4.40E-02
hsa_circ_0089763	M	−1.98	2.43E-02
hsa_circ_0006940	14	−2.35	2.96E-02
hsa_circ_0004489	14	−2.45	1.84E-02
hsa_circ_0031772	14	−2.48	1.08E-02
hsa_circ_0055902	2	−3.03	1.46E-04
hsa_circ_0022568	11	−3.29	1.13E-02
hsa_circ_0071320	4	−3.43	2.60E-03
hsa_circ_0002571	14	−3.67	2.20E-03
hsa_circ_0040412	16	−4.35	7.55E-05
hsa_circ_0052884	2	−4.42	8.04E-03
hsa_circ_0008442	1	−4.71	4.12E-02
hsa_circ_0007636	1	−4.77	3.48E-02
hsa_circ_0069967	4	−5.12	1.01E-04
hsa_circ_0022547	11	−5.64	1.08E-02
hsa_circ_0069970	4	−5.81	6.97E-05
hsa_circ_0034138	15	−5.91	4.11E-04
hsa_circ_0092300	2	−6.18	4.22E-04
hsa_circ_0092342	11	−6.77	4.34E-02
hsa_circ_0001853	9	−7.36	5.60E-05
hsa_circ_0092280	1	−7.72	2.17E-03
hsa_circ_0004287	11	−8.52	4.90E-05
hsa_circ_0092282	1	−8.66	1.84E-05
hsa_circ_0092275	1	−9.62	4.47E-03
hsa_circ_0007319	7	−9.86	4.85E-07
hsa_circ_0039972	16	−10.98	3.05E-05
hsa_circ_0007956	18	−12.27	3.78E-04
hsa_circ_0034121	15	−12.37	2.80E-03
hsa_circ_0024019	11	−12.37	1.24E-04
hsa_circ_0024018	11	−12.67	1.11E-04
hsa_circ_0034118	15	−14.24	2.70E-04
hsa_circ_0043980	17	−16.26	1.07E-03
hsa_circ_0092360	17	−27.80	9.02E-03
hsa_circ_0076872	6	−43.61	4.85E-07
hsa_circ_0035407	15	−994.94	7.76E-11
hsa_circ_0035409	15	−1234.90	1.96E-07
hsa_circ_0006257	12	−27596.01	4.85E-07

Feature ID	Chromosome	Fold change	FDR
hsa_circ_0015637	1	556.31	8.94E-09
hsa_circ_0015774	1	515.70	2.74E-07
hsa_circ_0087119	9	314.69	2.71E-03
hsa_circ_0040679	16	258.13	4.88E-08
hsa_circ_0087948	9	253.91	3.36E-07
hsa_circ_0008347	19	88.59	2.08E-05
hsa_circ_0069969	4	32.75	4.85E-02
hsa_circ_0006061	1	27.89	1.87E-04
hsa_circ_0043602	17	13.55	5.26E-03
hsa_circ_0043601	17	13.49	5.26E-03
hsa_circ_0043605	17	13.24	4.89E-03
hsa_circ_0043604	17	13.09	4.94E-03
hsa_circ_0043603	17	13.05	5.89E-03
hsa_circ_0009016	11	7.27	1.64E-03
hsa_circ_0031772	14	−2.24	1.14E-02
hsa_circ_0063778	22	−2.37	9.10E-03
hsa_circ_0055902	2	−2.48	1.75E-02
hsa_circ_0006940	14	−2.49	1.38E-02
hsa_circ_0004489	14	−2.60	1.38E-02
hsa_circ_0089763	M	−2.96	1.21E-03
hsa_circ_0000705	16	−2.97	4.25E-03
hsa_circ_0002978	1	−3.04	2.56E-02
hsa_circ_0008733	1	−3.04	2.72E-02
hsa_circ_0006643	1	−3.04	2.39E-02
hsa_circ_0004784	1	−3.05	2.52E-02
hsa_circ_0081371	7	−3.17	5.16E-03
hsa_circ_0052884	2	−3.39	1.91E-03
hsa_circ_0002571	14	−3.50	4.16E-03
hsa_circ_0001853	9	−3.68	2.89E-03
hsa_circ_0090906	X	−3.71	1.12E-02
hsa_circ_0034138	15	−3.86	2.86E-03
hsa_circ_0034118	15	−3.94	6.64E-03
hsa_circ_0022568	11	−4.34	5.88E-03
hsa_circ_0004287	11	−4.83	1.05E-03
hsa_circ_0010166	1	−4.92	3.53E-03
hsa_circ_0092275	1	−4.94	6.76E-03
hsa_circ_0040412	16	−5.00	2.97E-04
hsa_circ_0008442	1	−5.31	2.15E-02
hsa_circ_0007636	1	−5.38	2.08E-02
hsa_circ_0092282	1	−5.55	3.43E-04
hsa_circ_0069967	4	−6.01	7.74E-05
hsa_circ_0092342	11	−6.18	3.14E-02
hsa_circ_0007319	7	−6.26	2.30E-06
hsa_circ_0092300	2	−6.59	2.29E-03
hsa_circ_0034117	15	−6.66	3.19E-03
hsa_circ_0022547	11	−6.69	6.43E-03
hsa_circ_0092280	1	−6.87	3.00E-03
hsa_circ_0071320	4	−8.06	4.03E-04
hsa_circ_0034121	15	−8.26	4.71E-03
hsa_circ_0069970	4	−9.34	4.64E-05
hsa_circ_0039972	16	−10.95	9.20E-05
hsa_circ_0024018	11	−11.52	4.20E-04
hsa_circ_0024019	11	−11.60	4.03E-04
hsa_circ_0007956	18	−13.18	3.43E-04
hsa_circ_0043980	17	−15.09	1.13E-03
hsa_circ_0092360	17	−29.19	7.77E-05
hsa_circ_0076872	6	−46.60	1.73E-07
hsa_circ_0035407	15	−622.97	4.30E-05
hsa_circ_0035409	15	−810.36	3.04E-05
hsa_circ_0006257	12	−19578.54	1.03E-06

Gene name	Gene type	Chromosome	Fold change	FDR
MT-TP	Mt_tRNA	M	31.48	6.80E-07
MT-TS1	Mt_tRNA	M	26.18	2.11E-06
MT-TT	Mt_tRNA	M	13.18	8.81E-03
MT-TS2	Mt_tRNA	M	−3.77	2.52E-03
SNORD121B	snoRNA	9	−10.05	4.43E-04
SNORD37	snoRNA	19	−11.78	6.27E-05

Gene name	Gene type	Chromosome	Fold change	FDR
MT-TS1	Mt_tRNA	M	45.05	4.11E-10
MT-TP	Mt_tRNA	M	38.27	3.33E-09
MT-TH	Mt_tRNA	M	−1.56	3.48E-02
MT-TI	Mt_tRNA	M	−2.05	4.25E-02
MT-TL1	Mt_tRNA	M	−2.19	9.59E-03
MT-TK	Mt_tRNA	M	−4.03	9.31E-04
MT-TS2	Mt_tRNA	M	−6.09	5.28E-05
SNORD115-31	snoRNA	15	−9.48	3.45E-03
SNORD37	snoRNA	19	−13.81	8.28E-06
SNORD121B	snoRNA	9	−15.21	6.44E-07

Gene name	Gene type	Chromosome	Fold change	FDR
MT-TP	Mt_tRNA	M	20.68	6.96E-09
MT-TS1	Mt_tRNA	M	12.82	1.34E-06
MT-TT	Mt_tRNA	M	12.23	3.65E-05
MT-TL2	Mt_tRNA	M	10.90	8.32E-05
MT-TQ	Mt_tRNA	M	8.34	1.11E-07
MT-TN	Mt_tRNA	M	7.23	2.23E-05
MT-TV	Mt_tRNA	M	5.11	1.74E-02
MT-TM	Mt_tRNA	M	4.95	1.00E-03
MT-TG	Mt_tRNA	M	4.23	2.25E-02
MT-TC	Mt_tRNA	M	4.21	1.76E-06
MT-TE	Mt_tRNA	M	3.05	3.94E-04
MT-TS2	Mt_tRNA	M	−3.23	1.50E-04
SNORD115-31	snoRNA	15	−4.34	5.04E-04
SNORD121B	snoRNA	9	−6.87	1.24E-07
SNORD121A	snoRNA	9	−7.45	1.11E-07
SNORD37	snoRNA	19	−8.32	1.12E-07

Gene name	Gene type	Chromosome	Fold change	FDR
MT-TP	Mt_tRNA	M	27.11	5.90E-07
MT-TS1	Mt_tRNA	M	25.43	5.13E-06
MT-TT	Mt_tRNA	M	12.34	7.07E-05
MT-TQ	Mt_tRNA	M	11.95	1.47E-04
MT-TN	Mt_tRNA	M	11.56	8.95E-04
MT-TL2	Mt_tRNA	M	10.88	7.37E-05
MT-TC	Mt_tRNA	M	7.62	3.19E-03
MT-TG	Mt_tRNA	M	5.24	1.04E-02
MT-TE	Mt_tRNA	M	4.52	1.84E-03
MT-TV	Mt_tRNA	M	4.19	2.14E-02
MT-TM	Mt_tRNA	M	4.18	1.23E-02
MT-TS2	Mt_tRNA	M	−3.29	1.60E-03
SNORD115-31	snoRNA	15	−4.42	7.03E-04
SNORD121B	snoRNA	9	−8.06	1.65E-05
SNORD37	snoRNA	19	−15.97	1.10E-07

Gene name	Gene type	Chromosome	Fold change	FDR
MT-TP	Mt_tRNA	M	21.76	1.42E-05
MT-TS1	Mt_tRNA	M	19.48	3.85E-05
MT-TT	Mt_tRNA	M	10.44	6.55E-05
MT-TQ	Mt_tRNA	M	8.22	2.66E-03
MT-TC	Mt_tRNA	M	2.58	2.29E-02
MT-TS2	Mt_tRNA	M	−4.32	1.27E-03
SNORD115-31	snoRNA	15	−4.75	4.10E-02
SNORD121B	snoRNA	9	−11.02	1.33E-05
SNORD37	snoRNA	19	−17.68	1.44E-05

PERMALINK

Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs

Srinivas V Koduru

Ashley N Leberfinger

Yuka I Kawasawa

Milind Mahajan

Niraj J Gusani

Arun J Sanyal

Dino J Ravnic

Abstract

Introduction

Materials and Methods

Read Alignment and Annotations

HCC and Normal Liver Tissue Samples

MicroRNA Profiling Using NanoString nCounter miRNA Assays

NanoString nCounter miRNA Data Analysis

Biological Processes and Gene Network Visualization by MetaCore

Statistical Analysis

Ethics

Results

Differential Expression of miRNA in Cirrhosis, LGDN, HGDN, eHCC, and HCC Tissue Samples

Figure 1.

Table 1.

Table 5.

Table 2.

Table 3.

Table 4.

Validation of Differentially Expressed miRNAs in HCC Clinical Samples

Table 6.

Figure 2.

Figure 3.

Figure 4.

Differential Expression of piRNA in Cirrhosis, LGDN, HGDN, eHCC, and HCC Tissue Samples

Figure 5.

Table 10.

Table 7.

Table 8.

Table 9.

Table 11.

Differential Expression of lncRNA in Cirrhosis, LGDN, HGDN, eHCC, and HCC Tissue Samples

Figure 6.

Table 12.

Table 14.

Table 13.

Differential Expression of circRNA in Cirrhosis, LGDN, HGDN, eHCC, and HCC Tissue Samples

Figure 7.

Table 15.

Table 19.

Table 16.

Table 17.

Table 18.

Differential Expression of sno/mt-RNA in Cirrhosis, LGDN, HGDN, eHCC, and HCC Tissue Samples

Table 23.

Figure 8.

Table 20.

Table 24.

Table 21.

Table 22.

Discussion

Electronic supplementary material

Acknowledgements

Author Contributions

Competing Interests

Footnotes

Contributor Information

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases