Dataset Information

Promoter Methylation of DNA Repair Genes Predicts Disease-free Survival of Gastric Adenocarcinoma after Adjuvant Radiotherapy.

ABSTRACT: The relentless debate on postoperative adjuvant radiotherapy in gastric adenocarcinoma (GA) has been lasting for decades. In this study, a new biomarker, named promoter methylation burden of DNA repair genes (RPMB), was established to identify the subgroup of patients who might benefit from adjuvant radiotherapy. Methylation profiles of 397 GA tumor samples were downloaded from The Cancer Genome Atlas (TCGA). RPMB for a patient was defined as the ratio of methylated DNA repair genes to the number of all DNA repair genes. Subgroup analyses in term of overall survival (OS) and disease-free survival (DFS) indicated that most of the subgroups favored the high-RMPB group. Kaplan-Meier analysis showed that overall the patients with high RPMB after R0 resection had a significantly better clinical outcome regarding DFS (hazard ratio [HR] = 0.013, p = 0.042). Additionally, high-RPMB patients, who underwent adjuvant radiotherapy with both ?T2 tumor and positive lymph nodes, showed superior DFS in comparison with the low-RPMB group (HR = 5.35 × 10-10, n = 26, p = 0.010). RPMB might be considered as a promising biomarker for decision-making with regard to postoperative adjuvant radiotherapy for GA patients.

SUBMITTER: An N

PROVIDER: S-EPMC7334297 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Promoter Methylation of DNA Repair Genes Predicts Disease-free Survival of Gastric Adenocarcinoma after Adjuvant Radiotherapy.

An Ning N Yu Zhuang Z He Xin-Jia XJ Zhao Yuan-Yuan YY Yu Li L Zhang Yong-Chun YC Lu Hai-Jun HJ Yang Xue X

Molecular therapy oncolytics 20200609

The relentless debate on postoperative adjuvant radiotherapy in gastric adenocarcinoma (GA) has been lasting for decades. In this study, a new biomarker, named promoter methylation burden of DNA repair genes (RPMB), was established to identify the subgroup of patients who might benefit from adjuvant radiotherapy. Methylation profiles of 397 GA tumor samples were downloaded from The Cancer Genome Atlas (TCGA). RPMB for a patient was defined as the ratio of methylated DNA repair genes to the numbe ...[more]

PMID: 32671186

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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

Promoter Methylation of DNA Repair Genes Predicts Disease-free Survival of Gastric Adenocarcinoma after Adjuvant Radiotherapy.

Publications

Promoter Methylation of DNA Repair Genes Predicts Disease-free Survival of Gastric Adenocarcinoma after Adjuvant Radiotherapy.

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