The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis

• Published in: EBioMedicine Vol. 2; no. 7; pp. 671 - 680
• Main Authors: Stark, Mitchell S., Klein, Kerenaftali, Weide, Benjamin, Haydu, Lauren E., Pflugfelder, Annette, Tang, Yue Hang, Palmer, Jane M., Whiteman, David C., Scolyer, Richard A., Mann, Graham J., Thompson, John F., Long, Georgina V., Barbour, Andrew P., Soyer, H. Peter, Garbe, Claus, Herington, Adrian, Pollock, Pamela M., Hayward, Nicholas K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2015; Elsevier
• Subjects: Adult; Biomarker; Cohort Studies; Diagnostic; Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Melanoma; Melanoma - blood; Melanoma - pathology; MicroRNA; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; MiRNA; Multivariate Analysis; Neoplasm Staging; Original; Predictive Value of Tests; Prognosis; Prognostic; Sensitivity and Specificity; Survival Analysis; Young Adult; Biomarker; RNA; AUROC; Diagnostic; HR; Prognostic; AUC; Ct; LDH; FFPE; AJCC; miRNA; M1a; M1c; M1b; USA; OR; MIA; CI; DOR; N stage; Melanoma; S100B; SMM; NA; MicroRNA; AGO2; miR; PD1; NM; CI, confidence interval; AUC, area under the curve; Ct, threshold cycle; M1c, metastasis to any other organs, OR distant spread to any site along with an elevated blood LDH level; NA, not applicable; AUROC, area under the receiver operator curve; PD1, programmed cell death protein; NM, nodular melanoma; S100B, S100 calcium-binding protein B; USA, United States of America; SMM, superficial spreading melanoma; FFPE, formalin-fixed paraffin-embedded; RNA, ribonucleic acid; M1b, metastasis to the lungs, with a normal blood LDH level; miR, microRNA; LDH, lactate dehydrogenase; MiRNA; HR, hazard ratio; N stage, nodal or number of lymph nodes stage; OR, odds ratio; miRNA, microRNA; DOR, diagnostic odds ratio; MIA, Melanoma Institute of Australia; M1a, metastasis to skin, subcutaneous (below the skin) tissue, or lymph nodes in distant parts of the body, with a normal blood LDH level; AJCC, American Joint Committee on Cancer; AGO2, argonaute RISC catalytic component 2
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2015.05.011

The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are <15%. Hence, melanoma detection in earlier stages (stages I–III) maximises the chances of patient survival. We measured the expression of a panel of 17 microRNAs (miRNAs) (MELmiR-17) in melanoma tissues (stage III; n=76 and IV; n=10) and serum samples (collected from controls with no melanoma, n=130; and patients with melanoma (stages I/II, n=86; III, n=50; and IV, n=119)) obtained from biobanks in Australia and Germany. In melanoma tissues, members of the ‘MELmiR-17’ panel were found to be predictors of stage, recurrence, and survival. Additionally, in a minimally-invasive blood test, a seven-miRNA panel (MELmiR-7) detected the presence of melanoma (relative to controls) with high sensitivity (93%) and specificity (≥82%) when ≥4 miRNAs were expressed. Moreover, the ‘MELmiR-7’ panel characterised overall survival of melanoma patients better than both serum LDH and S100B (delta log likelihood=11, p<0.001). This panel was found to be superior to currently used serological markers for melanoma progression, recurrence, and survival; and would be ideally suited to monitor tumour progression in patients diagnosed with early metastatic disease (stages IIIa–c/IV M1a–b) to detect relapse following surgical or adjuvant treatment. •A seven-miRNA panel (MELmiR-7) detected the presence of melanoma with high sensitivity (93%) and specificity (≥82%).•In serially collected stage IV specimens, members of the ‘MELmiR-7’ panel confirmed tumour progression in 100% of cases.•The ‘MELmiR-7’ panel is superior to currently used serological markers for melanoma progression, recurrence, and survival.