Identification of hub methylated‐CpG sites and associated genes in oral squamous cell carcinoma

Abstract

To improve personalized diagnosis and prognosis for oral squamous cell carcinoma (OSCC) by identification of hub methylated-CpG sites and associated genes, weighted gene comethylation network analysis (WGCNA) was performed to examine and identify hub modules and CpG sites correlated with OSCC. Here, WGCNA modeling yielded blue and brown comethylation modules that were significantly associated with OSCC status. Following screening of the differentially expressed genes (DEGs) from gene expression microarrays and differentially methylated-CpG sites (DCGs), integrated multiomics analysis of the DEGs, DCGs, and hub CpG sites from the modules was performed to investigate their correlations. Expression levels of 16 CpG sites-associated genes were negatively correlated with methylation patterns of promoter. Moreover, Kaplan-Meier survival analysis of the hub CpG sites and associated genes was carried out using 2 public databases, MethSurv and GEPIA.Only 5 genes, ACTA1, ACTN2, OSR1, SYNGR1, and ZNF677, had significant overall survival using GEPIA. Hypermethylated-CpG sites ACTN2-cg21376883 and OSR1-cg06509239 were found to be associated with poor survival by MethSurv.Methylation status of specific site and expression levels of associated genes were determined using clinical samples by quantitative methylation-specific PCR and real-time PCR. Pearson's correlation analysis showed that methylation levels of cg06509239 and cg18335068 were negatively related to OSR1 and ZNF677 expression levels, respectively. Our classification schema using multiomics analysis represents a screening framework for identification of hub CpG sites and associated genes. K E Y W O R D SCpG site, methylation, multiomics, oral squamous cell carcinoma, survival analysis, WGCNA | 3175 DAI et Al.

The remodelling of actin composition as a hallmark of cancer

“…The presence of ACTA1 expressing fibroblasts in the prostate cancer stroma is associated with increased tumour metastatic potential [31] . In the case of oral squamous cell carcinoma, high expression of ACTA1 is associated with shorter survival ( Table 1 ) [32] . Additionally, in basal-like breast cancer, ACTA1 is a biomarker that is associated with chemoresistance ( Table 1 ) [33] .…”

Identification of potential CpG sites for oral squamous cell carcinoma diagnosis via integrated analysis of DNA methylation and gene expression

“…Abnormal DNA methylation patterns, including hypermethylation of gene promoter region which is accompanied by gene silencing, play a key role in a large number of cancers [ 18 ]. Previous research revealed that the hub-methylated sites were related the diagnosis and prognosis for OSCC by weighted gene comethylation network analysis (WGCNA) [ 19 ]. To identify samples with CIMP, patients were clustered by K-means method in our study, and the results suggested that samples with CIMP had lower survival rate.…”

RPL19 Is a Prognostic Biomarker and Promotes Tumor Progression in Hepatocellular Carcinoma

“…carcinoma (Dai et al, 2020) and pancreatic cancer (Wang et al, 2020). In regard to HCC, many studies have been conducted to identify the hub genes correlated with its progression and prognosis.…”

“…Then, correlation analysis between these modules and different phenotypes was used to determine the molecular characteristics of the specific phenotype. To date, WGCNA has been used to explore hub genes and tumor biomarkers of many cancers, such as bladder cancer ( Jiang et al, 2020 ), prostate cancer ( Wei et al, 2020 ), oral squamous cell carcinoma ( Dai et al, 2020 ) and pancreatic cancer ( Wang et al, 2020 ). In regard to HCC, many studies have been conducted to identify the hub genes correlated with its progression and prognosis.…”