TABLE 1.

An overview of the studies’ characteristics included in the systematic review.

Study	Category of patients	City/Country	Number of patients	Methodology	Pathways analysis
Diez-Fraile et al., 2014	AMA	Ghent, Belgium	21	miRNA extraction using a silica-gel-based membrane purification method. RT-qPCR was performed and further validation of the results was conducted.	miRNA predicted targets and KEGG pathway analysis was evaluated employing the Mirpath bioinformatics tool available on the DIANA LAB website.
Moreno et al., 2015	AMA	Valencia, Spain	30	Presence, proportion and quality of miRNAs were assessed with small RNA LabChips and BioAnalyzer. miRNAs Microarray analysis was performed to compare the miRNA profiles. RT-qPCR was employed to confirm the results from the pooled microarrays.	Diana-miRPath was employed to perform pathways analysis.
Chen et al., 2015	POF	Changsha, China	6	Total RNA extraction was performed with TRIzol reagent and was subsequently reverse transcribed using RevertAid First Strand cDNA synthesis kit.	TargetScan and micrRNA website were employed to detect targeted genes. No pathway analysis was further performed.
Luo et al., 2019	POR	Tianjin, China	7	RNA extraction was performed and integrity of RNA was assessed. High-throughput RNA sequencing was performed. HiSeq results were annotated and classified in GenBank database. miRbase was employed to identify known miRNAs, while novel miRNAs were identified with Mireap software.	miRanda and TargetScan software were implemented to predict target genes, which were then annotated with GO and KEGG database.
Zhang K. et al., 2017	POR	Shanghai, China	30	RNA extraction was performed and RNA quality was checked. RNA was then purified and further validated with electrophoresis. miRNA sequencing was performed. cDNA libraries were prepared. The EB-Seq algorithm was applied to identify differentially expressed genes. Verification of miRNA and mRNA expression was conducted	Targetscan was implemented to predict miRNA targets. GO analysis was performed. Pathways analysis according to KEGG database was utilized to identify significant pathways. Additional miRNA-mRNA network analysis was performed.

miRNA, microRNA; RT-qPCR, Quantitative reverse transcription PCR; cDNA, complementary DNA; mRNA, messenger RNA; KEGG, Kyoto Encyclopedia of Genes and Genomes; GO, Gene Ontology.