Transcriptome-wide association study identifies multiple genes and pathways associated with pancreatic cancer

Liuyun Gong; Dan Zhang; Yutiantian Lei; Yuanjie Qian; Xinyue Tan; Suxia Han

doi:10.1002/cam4.1836

Transcriptome-wide association study identifies multiple genes and pathways associated with pancreatic cancer

Cancer Med. 2018 Nov;7(11):5727-5732. doi: 10.1002/cam4.1836. Epub 2018 Oct 18.

Authors

Liuyun Gong¹, Dan Zhang², Yutiantian Lei¹, Yuanjie Qian¹, Xinyue Tan¹, Suxia Han¹

Affiliations

¹ Department of Oncology, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
² Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Abstract

Aim: To identify novel candidate genes for pancreatic cancer.

Methods: We performed a transcriptome-wide association study (TWAS) analysis of pancreatic cancer (PC). GWAS summary data were driven from the published studies of PC, totally involving 558 542 SNPs in 1896 individuals with pancreatic cancer and 1939 healthy controls. FUSION software was applied to the PC GWAS summary data for tissue-related TWAS analysis, including whole blood, peripheral blood, adipose, and pancreas. The functional relevance of identified genes with PC was further validated by Oncomine, STRING, and CluePedia tool.

Results: Transcriptome-wide association study analysis identified 19 genes significantly associated with PC, such as LRP5L (P value = 5.21 × 10^-5 ), SOX4 (P value = 3.2 × 10^-4 ), and EGLN3 (P value = 6.2 × 10^-3 ). KEGG pathway enrichment analysis detected several PC-associated pathways, such as One carbon pool by folate (P value = 1.60 × 10^-16 ), Cell cycle (P value = 1.27 × 10^-7 ), TGF-beta signaling pathway (P value = 4.64 × 10^-6 ). Further comparing the 19 genes with previously identified overexpressed genes in PC patients found one overlapped gene SOX4.

Conclusion: We identified some novel candidate genes and pathways associated with PC. Our results provide novel clues for the genetic mechanism studies of pancreatic cancer.

Keywords: genome-wide association study; pancreatic cancer; transcriptome-wide association study.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Female
Gene Expression Profiling / methods*
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks*
Genetic Predisposition to Disease
Genome-Wide Association Study / methods*
Humans
Pancreatic Neoplasms / genetics*
Polymorphism, Single Nucleotide
Software

Substances

Biomarkers, Tumor