Novel methylation-driven genes identified as prognostic indicators for lung squamous cell carcinoma.

Lung cancer remains the leading cause of cancer death. DNA methylation plays an essential role in carcinogenesis through regulating gene expression and gene alternative splicing. However, the role of methylation in the tumorigenesis of lung squamous cell carcinoma (SCC) and its association with prognosis remains unclear. Here, we used an integrative approach to evaluate the prognostic value of epigenetic processes in lung SCC by examining the data provided by The Cancer Genome Atlas (TCGA). We found that the mean methylation level was significantly decreased in lung SCC. We also identified methylation-driven genes which were associated with cancer-related pathways. The multivariate Cox regression analysis showed four methylation-driven genes, GCSAM, GPR75, NHLRC1, and TRIM58, could be served as prognostic indicators for lung SCC. Validation on two external GEO datasets showed consistent methylation alterations of the four genes. These findings may have important implications in the understanding of the potential therapeutic method for lung SCC.