Aberrant CpG‐methylation affects genes expression predicting survival in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is a common diagnosed disease with high‐mortality rate, and its prognostic implications are under discovered. DNA methylation aberrations are not only an important event for dysregulation of gene expression during tumorigenesis but also a revolution in epigenetics by identifying key prognostic biomarkers for multiple cancers. In this study, we analyzed methylation status of 485 578 CpG sites and RNA‐seq transcriptomes of 20 532 genes for 1095 LUAD samples in TCGA database. The association between DNA methylation and the prognostic value of the corresponding gene expression was identified as well. In total, ten aberrantly methylated and dysregulated genes (AURKA, BLK, CNTN2, HMGA1, PTTG1, TNS4, DAPK2, MFSD2A, THSD1, and WNT7A) were highlighted which were significantly correlated with overall survival of 492 LUAD patients, which were all reported as tumor‐associated genes in other various cancers and worthy of further investigated and might be used as therapeutic targets for LUAD. Together, methylation aberrances regulate gene expression level during tumorigenesis and influence prognosis of LUAD patients. Integrating knowledge of epigenetics and expression of genes can be useful for an in‐depth understanding of cancer mechanism and for the eventual purpose of precisely prognostic and therapeutic target verification.

[Retracted] Aberrant Methylation and Differential Expression of SLC2A1, TNS4, GAPDH, ATP8A2, and CASZ1 Are Associated with the Prognosis of Lung Adenocarcinoma

“…de Almeida and other colleagues [ 14 ] analyzed the DNA methylation and gene expression data between breast cancer tissue and corresponding normal tissue in TCGA and found that cg12374721 (PRAC2), cg18081940 (TDRD10), and cg04475027 (TMEM132C) could be used as diagnostic and prognostic markers in breast cancer. He and other experts [ 21 ] analyzed the methylation status of CpG sites and the RNA-seq data of LUAD in TCGA database to explore the relationship regarding the prognostic value between DNA methylation and corresponding gene expression, and then 10 genes were found to be related to the prognosis of patients, indicating that they may be therapeutic targets of LUAD. Although there have been studies on biomarkers for prognosis of LUAD, most of the biomarkers cannot help to accurately predict the prognosis of patients with LUAD.…”

Genome-Wide Analysis of Lung Adenocarcinoma Identifies Novel Prognostic Factors and a Prognostic Score

“…The past decade has witnessed rapid progress in next-generation sequencing and its increasing application in preclinical practice. In recent years, several studies have attempted to associate the transcriptome or epigenome with the clinical outcomes of patients with LUAD (Selamat et al, 2012; Zhang et al, 2017; Gao et al, 2018; He et al, 2018). Zhang et al analyzed and validated the expression profiles and prognostic values of the mRNAs of five differentially expressed genes associated with DNA methylation in LUAD (Zhang et al, 2017), increasing the likelihood that altered signature genes will become useful biomarkers.…”

“…Zhang et al analyzed and validated the expression profiles and prognostic values of the mRNAs of five differentially expressed genes associated with DNA methylation in LUAD (Zhang et al, 2017), increasing the likelihood that altered signature genes will become useful biomarkers. Using a TCGA dataset, He et al (2018) disentangled the relationships between aberrant CpG-methylation and gene expression to identify 10 aberrantly methylated and dysregulated genes. However, their study only focused on the ability of individual genes to predict OS.…”

“…For instance, using genome-scale DNA methylation profiling, a study identified 164 hypermethylated genes and 57 hypomethylated genes involved in cell differentiation and the epithelial-to-mesenchymal transition in LUAD (Selamat et al, 2012). Notably, DNA methylation also accounts for the alteration of gene expression in LUAD (Zhang et al, 2017; Gao et al, 2018; He et al, 2018), and may thus indirectly affect the biological behaviors and processes of LUAD. Specifically, He et al (2018) identified an association between aberrant CpG-methylation and the prognostic value of the corresponding gene expression based on 1095 LUAD samples, and identified 10 aberrantly methylated and dysregulated genes with independent prognostic value.…”

InterTADs: Integration of Multi-Omics Data on Topological Associated Domains

“…is remaining a promising field since there is no widely accepted approach for it. The most common processes to compare different omics data are by (i) comparing the gene lists produced at the end of each individual analysis, with the assumption that overlapping genes were influenced by different mechanisms (6,7) and (ii) checking the correlation of two events that are associated with the same gene, using statistical methods such as spearman or pearson correlation test (8,9). However, as interactions in biological systems are generally not linear, methods such as PCA, Bayesian or non-Bayesian networkbased were applied as extended data integration approaches (10).…”