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.

Integral Analysis of the RNA Binding Protein-associated Prognostic Model for Renal Cell Carcinoma

“…DDX47 is involved in maintenance of genome stability via interacting with FANCD2 to lower R-loop levels [28], and study has revealed that overexpression of DDX47 induces tumor cells apoptosis [29]. DQX1, acting as the methylation-driven genes, is a novel prognostic marker in lung squamous cell carcinoma [30]. EXOSC5 could promotes growth of colorectal cancer through regulating ERK and AKT pathways [31].…”

Pan-Cancer Methylated Dysregulation of Long Non-coding RNAs Reveals Epigenetic Biomarkers

“…CYP1B1-AS1 has been confirmed to play an important role in triple-negative breast cancer, lung adenocarcinoma and acute myeloid leukemia, and was associated with the prognosis of these cancers ( Cheng et al, 2021 ; Ren et al, 2021 ; Vishnubalaji and Alajez, 2021 ). Abnormal methylation and low expression of CTC-523E23 led to poor prognosis in patients with lung squamous cell carcinoma ( Rui Li et al, 2020 ). Inhibition of LINC01010 may promote the migration and invasion of lung cancer cells ( Cao et al, 2020 ) and help in the prediction of neuroblastoma prognosis ( Gao et al, 2020 ).…”

Potential Genes Associated with the Survival of Lung Adenocarcinoma Were Identified by Methylation

“…The Cox regression model was used to further analyze the predictive genes screened by the linear mixed model and to explore the relationship between methylation-driven genes and the prognosis of LUAD [ 36 ]. It is still assumed that all the markers may be involved in the development of LUAD, and the effect size of each gene should follow a normal distribution: …”