MIR375 hypermethylation as a prognostic predictor for head and neck squamous cell carcinoma: Insights from The Cancer Genome Atlas (TCGA)

Abstract

Objective: To conduct exploratory bioinformatics analyses of the potential prognostic value of DNA methylation patterns in MIR375 regulatory regions and of expression levels of its encoded microRNA, hsa‑miR‑375 (miR375), in head and neck squamous cell carcinoma (HNSCC). Design: Data from 490 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA), 50 of which were paired non-tumor surgical margins. Clinicopathological data, DNA methylation data from regions associated with MIR375, and miR-375 expression data were analyzed. Kaplan-Meier curves and Cox regression analyses were used to determine overall survival (OS) and disease-free survival (DFS) at 5 years in each group. Results: Differentially methylated regions were associated with miR-375 expression in HNSCC. Specially, hypermethylation in N shore region was independently associated with poor OS and DFS. After adjusting for methylation patterns in other regions and miR-375 expression, these associations remained significant. DFS was also associated with methylation patterns in the enhancer region. After adjusting for confounding factors (the most robust model), hypermethylation in the N shore region was found to be an unfavorable predictor of OS and DFS. Clinicopathological and lifestyle factors also influenced the OS and DFS rates. Conclusions: Methylation in DNA regions that may influence MIR375 transcription can be considered as predictors of OS and DFS in HNSCC, particularly those in the N shore region. This region should be a target for future investigations into MIR375 methylation pattern and its role in modulating miR-375 expression in HNSCC.