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High expression of Annexin A2 is associated with DNA repair, metabolic alteration, and worse survival in pancreatic ductal adenocarcinoma.

ABSTRACT: BACKGROUND:Annexin A2 (ANXA2) is a known driver of cancer progression. We investigated what mechanism associates with ANXA2 high expression and its survival impact using a bioinformatic approach in pancreatic ductal adenocarcinoma. METHODS:Primary pancreatic tumor (n = 185) cohort in The Cancer Genome Atlas and Gene set enrichment analysis were used. RESULTS:There were no significant associations between ANXA2 expression and clinicopathologic features of the patients investigated. The ANXA2 high tumors enriched some of the known downstream signaling, such as NF-?B (P = .028) and tumor necrosis factor (P = .044) pathways, whereas others, such as angiogenesis or epithelial-mesenchymal transition, were not associated. ANXA2 high expression tumors enriched DNA repair-related gene sets (DNA repair; P = .011, p53 pathway; P = .036) and cell proliferation-related gene sets (MYC targets; P = .041). In addition, new association with metabolism related gene sets, such as glycolysis (P = .016), nucleic acid metabolism (P = .001), and pyrimidine metabolism (P = .004) were identified in the ANXA2 high group. Patients with high ANXA2 expression demonstrated significantly worse disease-free survival (P = .001) and overall survival (P = .014), with high ANXA2 being an independent risk factor. CONCLUSION:High ANXA2 expression was associated with NF-?B and tumor necrosis factor signaling, DNA repair, cell proliferation, and metabolic alteration and worse prognosis in pancreatic ductal adenocarcinoma.

SUBMITTER: Takahashi H

PROVIDER: S-EPMC6661011 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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High expression of Annexin A2 is associated with DNA repair, metabolic alteration, and worse survival in pancreatic ductal adenocarcinoma.

Takahashi Hideo H Katsuta Eriko E Yan Li L Dasgupta Subhamoy S Takabe Kazuaki K

Surgery 20190603 2

<h4>Background</h4>Annexin A2 (ANXA2) is a known driver of cancer progression. We investigated what mechanism associates with ANXA2 high expression and its survival impact using a bioinformatic approach in pancreatic ductal adenocarcinoma.<h4>Methods</h4>Primary pancreatic tumor (n = 185) cohort in The Cancer Genome Atlas and Gene set enrichment analysis were used.<h4>Results</h4>There were no significant associations between ANXA2 expression and clinicopathologic features of the patients invest ...[more]

PMID: 31171367

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Project description:Background:Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies due to its high morbidity and mortality. DNA methylation exerts a vital part in the development of PDAC. However, a mechanistic role of mutual interactions between DNA methylation and mRNA as epigenetic regulators on transcriptomic alterations and its correlation with clinical outcomes such as survival have remained largely uncovered in cancer. Therefore, elucidation of aberrant epigenetic alteration in the development of PDAC is an urgent problem to be solved. In this work, we conduct an integrative epigenetic analysis of PDAC to identify aberrant DNA methylation-driven cancer genes during the occurrence of cancer. Methods:DNA methylation matrix and mRNA profile were obtained from the TCGA database. The integration of methylation and gene expression datasets was analyzed using an R package MethylMix. The genes with hypomethylation/hypermethylation were further validated in the Kaplan-Meier analysis. The correlation analysis of gene expression and aberrant DNA methylation was also conducted. We performed a pathway analysis on aberrant DNG methylation genes identified by MethylMix criteria using ConsensusPathDB. Results:188 patients with both methylation data and mRNA data were considered eligible. A mixture model was constructed, and differential methylation genes in normal and tumor groups using the Wilcoxon rank test was performed. With the inclusion criteria, 95 differential methylation genes were detected. Among these genes, 74 hypermethylation and 21 hypomethylation genes were found. The pathway analysis revealed an increase in hypermethylation of genes involved in ATP-sensitive potassium channels, Robo4, and VEGF signaling pathways crosstalk, and generic transcription pathway. Conclusion:Integrated analysis of the aberrant epigenetic alteration in pancreatic ductal adenocarcinoma indicated that differentially methylated genes could play a vital role in the occurrence of PDAC by bioinformatics analysis. The present work can help clinicians to elaborate on the function of differentially methylated expressed genes and pathways in PDAC. CDO1, GJD2, ID4, NOL4, PAX6, TRIM58, and ZNF382 might act as aberrantly DNA-methylated biomarkers for early screening and therapy of PDAC in the future.

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Dataset Information

High expression of Annexin A2 is associated with DNA repair, metabolic alteration, and worse survival in pancreatic ductal adenocarcinoma.

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High expression of Annexin A2 is associated with DNA repair, metabolic alteration, and worse survival in pancreatic ductal adenocarcinoma.

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