Table 8.
MiRNA signatures in rectal cancer patients receiving neoadjuvant chemoradiation.
| First Author and Year | Tumor | Overall Population (Treated Patients) | Treatment | Samples | Markers | Methods | Response to Treatment | Other Findings |
|---|---|---|---|---|---|---|---|---|
| Gaedcke, J., 2012 [95] | Rectal cancer | 57 (57) | Chemoradiation | Tumor tissues | miR-135b | Microarray | Not examined | MiR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p were differentially expressed between rectal and colon cancer tissues. MiR-135b expression correlated with tumor regression grade, disease-free survival and cancer-specific survival |
| Drebber, U., 2011 [96] | Rectal cancer | 40 (40) | Chemoradiation | Tumor tissues | miR-21, miR-143 and miR-145 | Real-time PCR | Compared to pre-treatment tissues, miR-21 was downregulated while miR-143 and miR-145 were upregulated in post-treatment tissues. MiR-145 downregulation was associated with worse response to neoadjuvant therapy | MiR-21 was upregulated in tumor tissue than in adjacent normal mucosa |
| Svoboda, M., 2012 [97] | Rectal cancer | 20 (20) | Chemoradiation | Tumor tissues | miR-215, miR-190b, miR-29b-2, let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a | Microarray and Real-time PCR | Eight miRNAs were differentially expressed between responders and non-responders. MiR-215, miR-190b and miR-29b-2 were upregulated in non-responders, while let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a were upregulated in responders. This 8-miRNA signature allowed to correctly classify 90% of non-responders | NA |
| Kheirelseid, E.A., 2012 [98] | Rectal cancer | 12 (12) | Chemoradiation | Tumor tissues | miR-16, miR-590-5p, miR-153, miR-519c-3p, and miR-561 | Microarray and Real-time PCR | A 3-miRNA signature (miR-16, miR-590-5p and miR-153) predicted incomplete response to neoadjuvant therapy. A 2-miRNA signature (miR-519c-3p and miR-561) predicted poor response to neoadjuvant therapy with an accuracy of 100% | NA |
| Della Vittoria Scarpati, G., 2012 [99] | Rectal cancer | 38 (38) | Chemoradiation | Tumor tissues | miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909, miR-630, miR-765, miR-1274b, miR-720 | Microarray and Real-time PCR | 14 miRNAs were differentially expressed in patients with complete response. 11 miRNAs were upregulated (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909, miR-630, miR-765), while 2 miRNAs were downregulated (miR-1274b, miR-720). MiR-622 and miR-630 showed 100% sensitivity and specificity in discriminating patients with complete response | NA |
| Campayo, M., 2018 [100] | Rectal cancer | 96 (96) | Chemoradiation | Tumor tissues | 377 miRNAs including miR-21, miR-99b and miR-375 | Microarray and Real-time PCR | 8 miRNAs (let-7b, let-7e, miR-21, miR-99b, miR-183, miR-328, miR-375 and miR-483-5p) were differentially expressed across different tumor regression grades. The combination of miR-21, miR-99b and miR-375 allowed to discriminate patients with complete response to neoadjuvant therapy | MiR-21, miR-99b and miR-375 were associated with disease-free and overall survival. |
| Lopes-Ramos, C.M., 2014 [101] | Rectal cancer | Training cohort: 27 (27) Validation cohort: 16 (16) | Chemoradiation | Tumor tissues | miR-21-5p | RNA-seq and Real-time PCR | In the training set, four miRNAs were differentially expressed between complete and incomplete responders. In the validation set, miR-21-5p was upregulated in complete responders. MiR-21-5p expression level allowed the prediction of complete response to neoadjuvant therapy with a sensitivity of 78% and a specificity of 86% | NA |
| Caramés, C., 2016 [102] | Rectal cancer | 78 (78) | Chemoradiation | Tumor tissues | mir-31 | Real-time PCR | MiR-31 expression level were higher in patients with complete response than in those with poor response | MiR-31 upregulation was associated with poor pathological response and worse overall survival |
| D’Angelo, E., 2017 [103] | Rectal cancer | 38 (38) | Chemoradiation | Tumor tissues | miR-194 | Real-time PCR | MiR-194 was overexpressed in patients who responded to neoadjuvant chemoradiation | NA |
| Du, B., 2018 [104] | Rectal cancer | 38 (38) | Chemoradiation | Tumor tissues | 41 miRNAs | Microarray | 41 miRNAs were differentially expressed between complete and incomplete responders to neoadjuvant therapy. MiR‑548c‑5p/miR‑548d‑5p and miR‑663a regulated genes associate with rectal cancer, thereby modulating the complete response to neoadjuvant chemoradiation | NA |
| Luo, J., 2018 [105] | Rectal cancer | 55 (55) | Chemoradiation | Tumor tissues | miR-519b-3p | Real-time PCR | In patients receiving neoadjuvant therapy, miR-519b-3p expression was positively correlated with response to treatment. A functional analysis suggested that miR-519b-3p was directly involved in response to neoadjuvant chemoradiation in an ARID4B-dependent way | NA |
| Yu, J., 2016 [106] | Rectal cancer | 149 (149) | Chemoradiation | Tumor tissues and serum | miR-345 | Microarray and Real-time PCR | MiR-345 upregulation was associated with a worse response to treatment either in tissue or serum | MiR-345 downregulation in serum was associated with better recurrence-free survival |
| Menéndez, P., 2013 [107] | Rectal cancer | 28 (28) | Chemoradiation | Serum | miR-21 | Real-time PCR | Not examined | Serum miR-21 downregulation was associated with high risk of recurrence and death. MiR-21 expression was an independent predictor of overall survival |
| Hiyoshi, Y., 2017 [108] | Rectal cancer | 94 (94) | Chemoradiation | Serum | let-7b, miR-15b, miR-20a, miR-21, miR-29a, miR-92a, miR-122, miR-125b, miR-141, miR-143, miR-145, miR-155, miR-200c, miR-221, miR-345, miR-423, miR-425, miR-1246 |
Real-time PCR | Serum miR-143 expression was higher in responders than in non-responders. Serum miR-143 expression was an independent predictor of pathological response | NA |