Analysis of molecular pathways in pancreatic ductal adenocarcinomas with a bioinformatics approach.

Yan Wang,Yan Li

doi:10.7314/apjcp.2015.16.6.2561

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death worldwide. Our study aimed to reveal molecular mechanisms. Microarray data of GSE15471 (including 39 matching pairs of pancreatic tumor tissues and patient-matched normal tissues) was downloaded from Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) in PDAC tissues compared with normal tissues by limma package in R language. Then GO and KEGG pathway enrichment analyses were conducted with online DAVID. In addition, principal component analysis was performed and a protein-protein interaction network was constructed to study relationships between the DEGs through database STRING. A total of 532 DEGs were identified in the 38 PDAC tissues compared with 33 normal tissues. The results of principal component analysis of the top 20 DEGs could differentiate the PDAC tissues from normal tissues directly. In the PPI network, 8 of the 20 DEGs were all key genes of the collagen family. Additionally, FN1 (fibronectin 1) was also a hub node in the network. The genes of the collagen family as well as FN1 were significantly enriched in complement and coagulation cascades, ECM-receptor interaction and focal adhesion pathways. Our results suggest that genes of collagen family and FN1 may play an important role in PDAC progression. Meanwhile, these DEGs and enriched pathways, such as complement and coagulation cascades, ECM-receptor interaction and focal adhesion may be important molecular mechanisms involved in the development and progression of PDAC.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm that arising within the ductal of the pancreas, comprising over 85% of all pancreatic tumor cases (Li et al, 2004; Hezel et al, 2006)
We identified differentially expressed genes (DEGs) in PDAC tissues compared with normal tissues by limma package in R language
T30308 were found gathered in PDAC tissue sample clusters and normal tissue sample clusters respectively (Figure 2), which were unreasonable

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm that arising within the ductal of the pancreas, comprising over 85% of all pancreatic tumor cases (Li et al, 2004; Hezel et al, 2006). The standard care for the 20% of patients with localized disease is surgery followed by chemotherapy, and radiation in some cases (Neuhaus et al, 2008). Treatment has not improved substantially and has little effect on prolonging survival time (Michaud, 2004). The genetic and biology of PDAC remain unclear until now. Exploring the molecular mechanism may contribute to the development of effective therapeutic approaches for this disease

Methods

Results

Conclusion