Table 2.
Potential prognostic circulating miRNA biomarkers for melanoma. This table summarizes the miRNAs found to be differentially expressed in the circulation of metastatic melanoma patients compared to non-metastatic melanoma patients, and/or those whose up- or down-regulation correlates with poor prognosis, highlighting the technical variables that may lead to the lack of consistency between studies. Pastel blue rows refer to discovery/training patient cohorts. Pastel orange rows refer to independent validation patient cohorts. Stage 0 = Healthy controls. MiRNAs showing the same direction of change between multiple studies and/or have been verified using both a discovery and validation cohort are shown in green and those that additionally have used an acceptable normalization method and have been verified using an independent validation cohort are shown in green and are underlined. MiRNAs showing a different direction of change between studies are shown in red. Exogenous spike-in controls are shown in blue. Further details are given in Table S2.
| Ref. | miRNA Up-Regulated |
miRNA Down-Regulated |
Sample Type | Sample Distribution |
Normalization Method |
|---|---|---|---|---|---|
| [61] | MEL18 | MEL18 | Plasma | Stages I (4), II (18), III (4) and IV (4) | cel-miR-254 and osa-miR-414 |
| [62] | 13 miRNA (inc miR-193b-3p, miR-720) | 40 miRNA | Serum | Serum, serum pools, melanoma and normal tissue, cell lines, whole blood | cel-miR-39, cel-miR-54, cel-miR-238; Global mean normalization and RefFinder (5 miRNAs) |
| miR-193b-3p, miR-720 | - | Serum | Stages 0 (4), I (11), II (17), III (11), IV (9); healthy (30) | cel-miR-39, cel-miR-54, cel-miR-238; Global mean normalization and RefFinder (5 miRNAs) | |
| [63] | miR-199a-5p, miR-150, miR-424 | miR-15b, miR-33a | Serum | Stages I (34), II (13), III (8); recurred stages I (5), II (7), III (13) | Median normalization |
| miR-199a-5p, miR-150, miR-424 | miR-15b, miR-33a | Serum | Stage I (10), II (16), III (4); recurred stages I (0), stage II (12), III (8) | Median normalization | |
| [64] | - | miR-200c-3p | Plasma | Stage I–II (10), III (10), IV (10); healthy (32) | Global mean normalization and NormFinder |
| [67] | miR-15b, miR-425, miR-150 | miR-30d | Serum | 201 stages I, II and III recurred and non-recurred | miR-30c and miR-181a NormFinder |
| miR-15b, miR-425, miR-150 | miR-30d | Serum | 82 stages I, II and III recurred and non-recurred | miR-30c and miR-181a NormFinder |
|
| [71] | - | miR-16 | Serum | Stages I (30), II (30), III (30) and IV (30); cancer-free (120) | cel-miR-39 |
| [74] | - | miR-206 | Serum | Stages I/II (20), III/IV (40) | RNA U6 |
| [75] | miR-21 | - | Plasma | Stages 0–II (12), III (10), IV (4); 3-year recurrence-free-survival (4), preoperative postoperative; benign (2) & dysplastic nevus (4) | Not specified |
| [76] | miR-221 | - | Serum | Stages I, II, III and IV (90), healthy controls (not specified) | cel-miR-54 |
| [77] | miR-221 | - | Serum | Stages I/II (27), III/IV (45); healthy (54) | miR-16, cel-miR-54 |
| [81] | miR-210 | - | Plasma | Stages III (20), IV (26); healthy (6) | Standard curves generated by using five serially diluted melanoma cell RNA |
| miR-210 | - | Plasma | Stages III (60), IV (70) disease-free; stage III (46 recurred <2 years/42 recurred >5 years); healthy (35) | Standard curves generated by using five serially diluted melanoma cell RNA |