Dataset Information

An integrated analysis of DNA promoter methylation, microRNA regulation, and gene expression in gastric adenocarcinoma.

ABSTRACT:

Background

Gastric adenocarcinoma (GAC), a common type of gastric cancer, poses a significant public health threat worldwide. This study aimed to determine the transcriptional regulatory mechanisms of GAC.

Methods

HTSeq-FPKM raw data were obtained from The Cancer Genome Atlas Stomach Adenocarcinoma data collection. Subsequently, the limma package in R was used to identify differentially expressed genes (DEGs). Differentially methylated genes (DMGs), DEGs, and differentially expressed microRNAs (miRNAs) in normal, and tumor tissues of the same patients were screened and compared using R software tools. A functional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) for various DEGs, DMGs, promoter methylation, and miRNAs. DEG-specific methylation and transcription factors were analyzed using ENCODE ChIP-seq.

Results

DEGs were centrally modified by the histone trimethylation of lysine 27 on histone H3 (H3K27me3). Upstream transcription factors of DEGs were enriched in different ChIP-seq clusters, such as Forkhead Box M1, E2F Transcription Factor 4, and suppressor of zest 12. Integrated regulatory networks of DEGs, promoter methylation, and miRNAs were constructed. Two miRNAs (hsa-mir-1 and hsa-mir-133a) and four DEGs (A disintegrin and metalloproteinase domain 12, transcription factor AP-2 alpha, solute carrier family 5 member 7, and cadherin 19) separately played important roles in the integrated regulatory network. Therefore, these DEGs, DMGs, promoter methylation, and miRNAs may play an important role in GAC pathogenesis.

Conclusions

In summary, the present study results provide insights into the oncogenesis and progression of GAC, thus accelerating the development of novel targeted GAC therapies.

SUBMITTER: Huang H

PROVIDER: S-EPMC8506766 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

An integrated analysis of DNA promoter methylation, microRNA regulation, and gene expression in gastric adenocarcinoma.

Huang Hongyun H Xie Lang L Feng Xiaoxuan X Zheng Zheng Z Ouyang Juntao J Li Yan Y Yu Jinlong J

Annals of translational medicine 20210901 18

<h4>Background</h4>Gastric adenocarcinoma (GAC), a common type of gastric cancer, poses a significant public health threat worldwide. This study aimed to determine the transcriptional regulatory mechanisms of GAC.<h4>Methods</h4>HTSeq-FPKM raw data were obtained from The Cancer Genome Atlas Stomach Adenocarcinoma data collection. Subsequently, the limma package in R was used to identify differentially expressed genes (DEGs). Differentially methylated genes (DMGs), DEGs, and differentially expres ...[more]

PMID: 34733966

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Project description:Claudin‑3 expression is associated with gastric cancer progression, but the role of epigenetic modifications remains unclear. We investigated methylation of the claudin‑3 promoter and expression profiles in gastric adenocarcinoma and their associations with clinicopathological characteristics and prognosis of the patients. A total of 122 patients with advanced gastric cancer [stage IIB‑IV, with lymph node (LN) metastasis] were enrolled. Each patient provided 4 tissue samples: normal gastric epithelium, intestinal metaplasia, primary tumor and metastatic LN. Claudin‑3 protein expression was examined by immunohistochemistry. Claudin‑3 promoter methylation was determined by methylation‑specific PCR and verified by bisulfite sequencing PCR. Claudin‑3 mRNA expression was measured by real‑time PCR in a subset of cases, and its correlation with protein expression was analyzed using Spearman correlation. Kaplan‑Meier survival analysis was performed (log‑rank test). Factors associated with survival were identified by Cox regression. The strong expression rate of claudin‑3 in intestinal metaplasia, primary tumor, metastatic LN and normal gastric epithelium was 91.8, 58.2, 30.3 and 13.9%, respectively. The promoter hypermethylation rate in intestinal metaplasia, primary tumor, normal gastric epithelium and metastatic LN was 5.7, 27.9, 36.9 and 49.2%, respectively. Claudin‑3 mRNA and protein expression were positively correlated (P<0.001) with normal gastric epithelium (rs=0.745), intestinal metaplasia (rs=0.876), primary gastric adenocarcinoma (rs=0.915) and metastatic LN (rs=0.819). Claudin‑3 mRNA expression was negatively correlated with claudin‑3 promoter methylation. Median patient survival was 38, 22 and 11 months in the hypomethylated, partially methylated and hypermethylated groups, respectively (P<0.001). Claudin‑3 promoter methylation status (HR: 5.67; 95% CI: 2.27‑14.17) but not claudin‑3 expression was an independent predictor of survival. Claudin‑3 promoter hypermethylation reduces claudin‑3 expression and independently predicts poor prognosis.

Dataset Information

An integrated analysis of DNA promoter methylation, microRNA regulation, and gene expression in gastric adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

An integrated analysis of DNA promoter methylation, microRNA regulation, and gene expression in gastric adenocarcinoma.

Similar Datasets

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