Integrative analysis of DNA methylation-driven genes for the prognosis of lung squamous cell carcinoma using MethylMix.

ABSTRACT

Background: DNA methylation acts as a key component in epigenetic modifications of genomic function and functions as disease-specific prognostic biomarkers for lung squamous cell carcinoma (LUSC). This present study aimed to identify methylation-driven genes as prognostic biomarkers for LUSC using bioinformatics analysis. Materials and Methods: Differentially expressed RNAs were obtained using the edge R package from 502 LUSC tissues and 49 adjacent non-LUSC tissues. Differentially methylated genes were obtained using the limma R package from 504 LUSC tissues and 69 adjacent non-LUSC tissues. The methylation-driven genes were obtained using the MethylMix R package from 500 LUSC tissues with matched DNA methylation data and gene expression data and 69 non-LUSC tissues with DNA methylation data. Gene ontology and ConsensusPathDB pathway analysis were performed to analyze the functional enrichment of methylation-driven genes. Univariate and multivariate Cox regression analyses were performed to identify the independent effect of differentially methylated genes for predicting the prognosis of LUSC. Results: A total of 44 methylation-driven genes were obtained. Univariate and multivariate Cox regression analyses showed that twelve aberrant methylated genes (ATP6V0CP3, AGGF1P3, RP11-264L1.4, HIST1H4K, LINC01158, CH17-140K24.1, CTC-523E23.14, ADCYAP1, COX11P1, TRIM58, FOXD4L6, CBLN1) were entered into a Cox predictive model associated with overall survival in LUSC patients. Methylation and gene expression combined survival analysis showed that the survival rate of hypermethylation and low-expression of DQX1 and WDR61 were low. The expression of DQX1 had a significantly negatively correlated with the methylation site cg02034222. Conclusion: Methylation-driven genes DQX1 and WDR61 might be potential biomarkers for predicting the prognosis of LUSC.