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Abstract 833: Integrative analysis of TCGA pancreatic ductal adenocarcinoma data

Pancreatic cancer is a heterogeneous type of cancer that exhibits different histopathological, molecular and genomic phenomena. Pancreatic ductal adenocarcinoma (PDAC) is the deadliest type of pancreatic cancer with a five-year survival of only 8%. Prognostic biomarkers for early detection of PDAC are not available. In this study, we used clinical, DNA methylation, and gene expression profiles of 146 TCGA PDAC patients. We analyzed the global patterns of DNA methylation and correlated the promoter DNA methylation with corresponding gene expression. CpG sites with a difference of 0.2 in the mean β value of the primary tumor and normal samples were considered as differentially methylated. We observed differential methylation of about 12-thousand CpG sites between tumor and normal samples, the majority of which are hypermethylated. Chromosome 1, 20, 18 and 19 are predominately hypermethylated and chromosome 9 is hypomethylated. CpG islands and regions that are in close proximity to CpG islands (shores) have more hypermethylated sites compared to the far away regions (shelf). Pathway enrichment analysis of differentially methylated genes enabled us to understand how changes in methylation affect biological pathways involved in the progression of PDAC. Our analysis reveals enrichment of MAPK signaling, Rap1 signaling, calcium signaling pathway, etc. Promoter DNA methylation is highly associated with its corresponding gene expression. A significant correlation between methylated CpG sites within 1.5kb from TSS and corresponding gene expression was observed between 4,971 CpGs and 1,744 corresponding genes, out of these about 92% of the genes showed a negative correlation. Survival analysis showed a statistically significant correlation between the expression levels of genes, NEK2, and ASPM with overall survival of the patients. In the future, we will further analyze the long non-coding RNA (lncRNA) promoter methylation, and role of lncRNA and miRNA in PDAC patients’ survival. Citation Format: Nitish K. Mishra, Siddesh Southekal, Chittibabu Guda. Integrative analysis of TCGA pancreatic ductal adenocarcinoma data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 833.