期刊
CANCER MEDICINE
卷 7, 期 11, 页码 5727-5732出版社
WILEY
DOI: 10.1002/cam4.1836
关键词
pancreatic cancer; genome-wide association study; transcriptome-wide association study
类别
资金
- National Natural Science Foundation of China [81672921]
- Innovation Capacity Support Plan of Shaanxi Province [2018TD-002]
Aim To identify novel candidate genes for pancreatic cancer. Methods Results 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. Transcriptome-wide association study analysis identified 19 genes significantly associated with PC, such as LRP5L (P value = 5.21 x 10(-5)), SOX4 (P value = 3.2 x 10(-4)), and EGLN3 (P value = 6.2 x 10(-3)). KEGG pathway enrichment analysis detected several PC-associated pathways, such as One carbon pool by folate (P value = 1.60 x 10(-16)), Cell cycle (P value = 1.27 x 10(-7)), TGF-beta signaling pathway (P value = 4.64 x 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.
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