Int J Med Sci 2020; 17(6):773-786. doi:10.7150/ijms.43272

Research Paper

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

Rui Li1, Yun-Hong Yin1, Jia Jin2, Xiao Liu1, Meng-Yu Zhang1, Yi-E Yang3✉, Yi-Qing Qu1✉

1. Department of Respiratory and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012, China.
2. Department of Cardiology, Zhangqiu District People's Hospital of Jinan, 250200, Shandong, China.
3. Department of Clinical Laboratory, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated with Shandong First Medical University, Jinan 250014, China.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Li R, Yin YH, Jin J, Liu X, Zhang MY, Yang YE, Qu YQ. Integrative analysis of DNA methylation-driven genes for the prognosis of lung squamous cell carcinoma using MethylMix. Int J Med Sci 2020; 17(6):773-786. doi:10.7150/ijms.43272. Available from http://www.medsci.org/v17p0773.htm

File import instruction

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.

Keywords: Lung squamous cell carcinoma, Methylation-driven genes, Biomarkers, A Cox predictive model, Overall survival