Table 2.
miRNA and lncRNA with potential roles in predicting therapy response and diagnosing resistance to cancer treatment
| Cancer type | ncRNAs | Function in therapy resistance | Sample type | Screening/training cohort sample size | Validation cohort sample size | SE/SP (training cohort; validation cohort) | AUC (training cohort/validation cohort) | Ref |
|---|---|---|---|---|---|---|---|---|
| Resistance to chemotherapy | ||||||||
| CRC | A signature including miR-20a, miR-130, miR-145, miR-216, and miR-372 | Downregulated in responders to oxaliplatin-based regimen | Serum | 40/40 | 173 | NA | 0.841/0.918 | 89 |
| mCRC | miR-130b, miR-106a, miR-484 | Overexpressed in patients with resistance to first-line 5-FU/oxaliplatin-based chemotherapy | Plasma | 24 | 150 | NA | NA | 90 |
| mCRC | miR-625-3p | Overexpressed in patients with poor response to XELOX/FOLFOX | Tumor tissue | 26 | 93 | NA | NA | 91 |
| Pancreatic cancer | miR-20a-5p | Abundant level predicts gemcitabine resistance | Plasma | 73 | NA | NA | 0.89 | 95 |
| HR+/HER2‐ breast cancer | miR-222, miR-20a, miR-451 | Overexpression of baseline miR-222, and upregulation of miR‐20a, and downregulation of miR-451 after 2nd cycle predict resistance to neoadjuvant chemotherapy | Plasma | 6 | 51 | NA | 0.706 for miR-222; 0.800 for miR-20a; 0.788 for miR-451 | 96 |
| Triple-negative breast cancer | miR-145-5p | Downregulated in patients who achieved pCR to cisplatin/doxorubicin-based chemotherapy | Tumor tissue | 32 | NA | NA | 0.7899 | 100 |
| Luminal breast cancers | miR-145 | Decreased in patients who respond to neoadjuvant chemotherapy | Serum | 56 | NA | NA | NA | 101 |
| Pediatric AML | miR-106a-3p/5p | Overexpressed in induction chemotherapy-resistant patients | NA | 637 | 666 | NA | NA | 102 |
| GC | A signature including miR- 9-5p, miR-9-3p, and miR-433-3p | Overexpressed in cisplatin-resistant patients | Serum | 74 | NA | 0.80/0.79 | 0.915/NA | 103 |
| Metastatic GC | miR-21 | Overexpressed in chemotherapy-resistant patients | Tumor tissue, plasma | 92 | NA | 0.88/0.69 | 0.83 | 104 |
| EC | miR-200c | Overexpressed in chemotherapy-resistant patients | Tumor tissue | 98 | NA | NA | NA | 105 |
| CRC | LncRNA XIST | Upregulated in patients with poor response to 5-FU | Tumor tissue, serum | 10/140 | 120 | 0.72/0.68 | NA/0.756 | 106 |
| CRC | MEG3 | Downregulated in CRC patients showing no response to oxaliplatin | Tumor tissue, serum | 8/160 | 140 | 0.72/0.61 | NA/0.784 | 107 |
| Breast cancer | A signature including AK291479, U79293, and BC032585 | Upregulation of lncRNAs AK291479 and BC032585 and downregulation of U79293 in patients with pCR to chemotherapy | Tissue | 488 | 614 | NA | 0.74 /0.72 | 108 |
| Ovarian cancer | A signature including eight lncRNAs | An eight-lncRNA signature associated with chemosensitivity to cisplatin | Tissue | NA/258 | 233 | NA | 0.83/0.67 | 109 |
| Resistance to target therapy | ||||||||
| Angiogenesis inhibitors | ||||||||
| mCRC | miR-126 | Upregulated in patients with resistance to XELOX chemotherapy combined with bevacizumab | Blood | 63 | NA | NA | NA | 111 |
| ER-positive breast cancer | Increased in patients with response to tamoxifen treatment | Tumor tissue | 12 | 81 | NA | NA | 115 | |
| Metastatic breast cancer | miR-20a-5p | Lower expression predicts benefit from bevacizumab | Tumor tissue | 115 | 203 | NA | NA | 116 |
| TKI and other small molecular inhibitors | ||||||||
| Lung cancers | A signature including miR-195, miR-122, miR-125, miR-21, and miR-25 | This signature can predict the EGFR mutational status and gefitinib sensitivity | Tumor tissue, plasma | 35 | 149 | NA | NA/0.869 | 117 |
| GISTs | miR-518e-5p | Increased in patients with secondary resistance to imatinib | Serum | 6 | 76 | 0.99/0.82 | NA/0.9938 | 119 |
| MM | miR-215-5p, miR-181a-5p, miR-376c-3p | Dysregulated in bortezomib-refractory patients | Serum | 30 | NA | 0.95/0.91 | 0.95 | 121 |
| Resistance to radiotherapy | ||||||||
| EC | miR-193b | Higher in patients who exhibited PR to radiotherapy | Serum | 75 | NA | NA | 0.71 | 122 |
| ESCC | rs4938723 in the promoter region of miR-34b/c | CC genotype favors a better response to CRT compared to TT + TC genotypes | Blood | 175 | NA | 0.85/0.71 | 0.777 | 123 |
| Locally advanced rectal adenocarcinoma | Signature including lnc-KLF7-1, lnc-MAB21L2-1, and LINC00324 | Classifying pCR to neoadjuvant CRT | Tumor tissue | 49 | NA | 0.91/0.94 | 0.93 | 124 |
| Resistance to immunotherapy | ||||||||
| HNSCC | A 25-miRNA-based signature | Predict TMB levels | Tumor tissue (TCGA) | 301 | 200 | 0.421/0.937; 0.36/0.863 | 0.822/0.702 | 129 |
| UCEC | A 26-miRNA-based signature | 311 | 207 | 0.682/0.915; 0.568/0.882 | 0.904/0.820 | 130 | ||
| Lung adenocarcinoma | A 25-miRNA-based signature | 267 | 177 | 0.77/0.96; 0.67/0.96 | 0.895/0.826 | 131 | ||
| Colon cancer | A 14-lncRNA signature | 195 | 195 | NA | 0.70/0.71 | 132 | ||
| Stomach adenocarcinoma | A 33-lncRNA-based signature | 261 | 87 | 0.83/0.96; 0.56/0.91 | 0.999/0.974 | 133 | ||
| ESCC | miR-1233-5p before treatment and miR-6885-5p, miR-4698, and miR-128-2-5p after treatment | Lower levels of miR-1233-5p before treatment and of miR-6885-5p, miR-4698, and miR-128-2-5p after treatment predict better response to nivolumab | Serum | 19 | NA | NA | 0.895; 0.93, 0.97;0.93, | 134 |
| NSCLC | Signature including miR-199a-3p, miR-21-5p, and miR-28-5p | Decreased in responders to anti-PD-1 or PD-L1 antibody | Plasma | 29 | 21 | NA | NA/0.925 | 135 |
5-FU Fluorouracil; AML Acute myeloid leukemia; AUC Area under the receiver operating characteristic curve; CRT Chemoradiotherapy; EC Esophageal cancer; ER Estrogen receptor; ESCC Esophageal squamous cell carcinoma; FOLFOX Folinic acid, fluorouracil and oxaliplatin; GC Gastric cancer; GISTs Gastrointestinal stromal tumors; HER2 Human epidermal growth factor receptor 2; HNSCC Head and neck squamous carcinoma; HR Hormone receptor; mCRC metastatic colorectal cancer; MM Multiple myeloma; NSCLC Non-small cell lung cancer; pCR Pathological complete response; PR Partial response; SE Sensibility; SP Specificity; TMB Tumor mutation burden; UCEC Uterine corpus endometrial carcinoma; XELOX Capecitabine + oxaliplatin.