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

Abstract

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.

Keywords: AGO2, argonaute RISC catalytic component 2; AJCC, American Joint Committee on Cancer; AUC, area under the curve; AUROC, area under the receiver operator curve; Biomarker; CI, confidence interval; Ct, threshold cycle; DOR, diagnostic odds ratio; Diagnostic; FFPE, formalin-fixed paraffin-embedded; HR, hazard ratio; LDH, lactate dehydrogenase; M1a, metastasis to skin, subcutaneous (below the skin) tissue, or lymph nodes in distant parts of the body, with a normal blood LDH level; M1b, metastasis to the lungs, with a normal blood LDH level; M1c, metastasis to any other organs, OR distant spread to any site along with an elevated blood LDH level; MIA, Melanoma Institute of Australia; Melanoma; MiRNA; MicroRNA; N stage, nodal or number of lymph nodes stage; NA, not applicable; NM, nodular melanoma; OR, odds ratio; PD1, programmed cell death protein; Prognostic; RNA, ribonucleic acid; S100B, S100 calcium-binding protein B; SMM, superficial spreading melanoma; USA, United States of America; miR, microRNA; miRNA, microRNA.

Fig. 1

Study summary.

Fig. 2

Expression of MELmiR-7 in stage IV progression patients.

Fig. 3

Conditional inference tree predicting survival outcomes.