Abstract
Introduction: Melanoma is the most fatal skin cancer with high risk of tumor relapse and poor prognosis. It is of clinical importance to identify novel molecular biomarkers to better understand the biology course of the disease and predict patient outcomes. In this study, we aimed to investigate the clinicopathological implications of miR-3127 expression in cutaneous melanomas.
Methods: We accessed The Human Cancer Atlas – Skin Cutaneous Melanoma (TCGA-SKCM) to analyze clinicopathological data, miRNA expression, mRNA expression, and DNA methylation of 470 melanoma patients. Differential expression analysis (DEA) was conducted to compare miRNA and mRNA expression between miR3127-low versus miR3127-high melanomas.
Results: Clustering analysis identified 317 miR3127-low and 129 miR3127-high cases. Patients with miR3127-high expression had worse progression-free survival (PFS) (p < 0.001) and overall survival (OS) (p = 0.011). DEA analysis demonstrated that large portions of genes in cell differentiation markers, cytokines, growth factors, translocated cancer genes, and oncogenes are differentially expressed by melanomas with low miR-3127 in comparison to those with high miR-3127 expression. Pathway analyses revealed that miR3127-high melanomas have higher activities of proliferation, DNA repair, and UV response but lower inflammation-related processes as compared to those with low mir-3127 expression. Methylation analyses showed no clear difference between the two groups.
Conclusion: This study demonstrated that melanomas with low and high miR-3127 expression have distinct tumor biology, gene expression profiling, and prognoses, which help facilitate our current understanding of the tumorigenesis of cutaneous melanomas and better predict the disease courses and patient survival.