Tumor miRNA Signatures Associate with Outcomes of Patients with Stage II/III Melanoma

Purpose: Patients with stage II and resected stage III melanomas have variable clinical outcomes, providing evidence of underlying biological differences in tumors and/or the patients themselves, beyond stage. The approval of adjuvant immunotherapy for stage IIB/C and resected stage III/IV disease (and adjuvant targeted therapy for resected stage III disease) has created a pressing need to develop biomarkers to accurately distinguish patients at low risk versus high risk for recurrence and death from melanoma. miRNAs are promising biomarkers because of their stability in tissues and fluids and their demonstrated functional and prognostic roles in melanoma. We hypothesized that miRNA expression could be integrated into prognostic models that would classify 5-year survival outcomes more accurately than clinical factors alone. Experimental Design: Using a NanoString miRNA Expression Assay, we analyzed 715 primary melanomas from patients with stage II or stage III disease within the InterMEL consortium and examined associations between miRNA expression and melanoma-specific death. Results: When integrated into clinical prognostic models for 5-year melanoma-specific survival, miRNA signatures improved the area under the receiver operating characteristic curve for patients in stage II from 0.71 for a “clinical factors–only” model to 0.81 for a “clinical plus miRNA” model in an independent test set, an improvement of 0.10 with a 95% confidence interval (0.03–0.19). The improvement was more modest for patients in stage III who were included in the analysis. Conclusions: Incorporating miRNA expression in primary melanomas may enhance the accuracy of clinical prognostic models and potentially aid in the selection of patients with melanoma for adjuvant treatment and clinical trials.