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MIR375 hypermethylation as a prognostic predictor for head and neck squamous cell carcinoma: Insights from The Cancer
Ana Carolina da Silva Lima1, Ileana Gabriela Sanghez de Rubió2, Shuting Lin3
1Nutritional Genomics Research Group, School of Nutrition, Federal University of Goiás, Goiânia, GO 74605-080, Brazil.
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 (miR-375), 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.
