Survival Analysis of Multi-Omics Data Identifies Potential Prognostic Markers of Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common and among the deadliest of pancreatic cancers. Its 5-year survival is only ∼8%. Pancreatic cancers are a heterogeneous group of diseases, of which PDAC is particularly aggressive. Like many other cancers, PDAC also starts as a pre-invasive precursor lesion (known as pancreatic intraepithelial neoplasia, PanIN), which offers an opportunity for both early detection and early treatment. Even advanced PDAC can benefit from prognostic biomarkers. However, reliable biomarkers for early diagnosis or those for prognosis of therapy remain an unfulfilled goal for PDAC. In this study, we selected 153 PDAC patients from the TCGA database and used their clinical, DNA methylation, gene expression, and micro-RNA (miRNA) and long non-coding RNA (lncRNA) expression data for multi-omics analysis. Differential methylations at about 12,000 CpG sites were observed in PDAC tumor genomes, with about 61% of them hypermethylated, predominantly in the promoter regions and in CpG-islands. We correlated promoter methylation and gene expression for mRNAs and identified 17 genes that were previously recognized as PDAC biomarkers. Similarly, several genes (B3GNT3, DMBT1, DEPDC1B) and lncRNAs (PVT1, and GATA6-AS) are strongly correlated with survival, which have not been reported in PDAC before. Other genes such as EFR3B, whose biological roles are not well known in mammals are also found to strongly associated with survival. We further identified 406 promoter methylation target loci associated with patients survival, including known esophageal squamous cell carcinoma biomarkers, cg03234186 (ZNF154), and cg02587316, cg18630667, and cg05020604 (ZNF382). Overall, this is one of the first studies that identified survival associated genes using multi-omics data from PDAC patients.

Identification of Key Genes for Nasopharyngeal Carcinoma by Gene Expression and DNA Methylation Data Integration Analysis

“…In addition, the distribution of few hypo-CpGs were comparatively even among shelfs, s-shore and CpG islands, except for higher in N-shore. Expectedly, we observed that the CpG island and its neighborhood location (shores) were predominantly hypermethylated which is similar with an early study 32,33 . The promoter regions (TSS, 1stExon and 5′UTR) had nearly twice hyper-CpGs (63.41% vs 36.59%) compared to outside of promoter regions (body and 3′UTR), similar observations were also reported by Nitish Kumar Mishra et.al 34 .…”

Construction of a Competitive Endogenous RNA Network for Pancreatic Adenocarcinoma Based on Weighted Gene Co-expression Network Analysis and a Prognosis Model

“…A system analysis based on the hypothesis of the mRNA-miRNA-lncRNA ceRNA network may lead to a molecular signature with better prognostic value in PAAD than a single gene. The multi-omics or meta-analysis has been applied to identify the biomarkers of pancreatic adenocarcinoma especially for PDAC (Chen et al, 2018a;Klett et al, 2018;Mishra et al, 2019). Mishra et al Identified survival associated genes using multiomics data from PDAC patients (Mishra et al, 2019).…”

“…The multi-omics or meta-analysis has been applied to identify the biomarkers of pancreatic adenocarcinoma especially for PDAC (Chen et al, 2018a;Klett et al, 2018;Mishra et al, 2019). Mishra et al Identified survival associated genes using multiomics data from PDAC patients (Mishra et al, 2019). And Klett et al identified 17 genes that were previously recognized as PDAC biomarkers (Klett et al, 2018) and several genes (B3GNT3, DMBT1, DEPDC1B) and lncRNAs (PVT1 and GATA6-AS) have FIGURE 4 | Kaplan-Meier survival curves of the training set, test set and total set.…”

Radiosensitization by Kinase Inhibition Revealed by Phosphoproteomic Analysis of Pancreatic Cancer Cells

“…Svenja Wiechmann 1,2,3 , Elena Saupp 4 , Daniela Schilling 4,5 , Stephanie Heinzlmeir 1 , Günter Schneider 6 , Roland M. Schmid 6 , Stephanie E. Combs 2,3,4,5 , Bernhard Kuster 1,2,3,7 , and Sophie Dobiasch 2,3,4,5,* Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers and known for its extensive genetic heterogeneity, high therapeutic resistance, and strong variation in intrinsic radiosensitivity. To understand the molecular mechanisms underlying radioresistance, we screened the phenotypic response of 38 PDAC cell lines to ionizing radiation.…”