Abstract
AimTo identify novel candidate genes for pancreatic cancer.MethodsWe 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.ResultsTranscriptome‐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.ConclusionWe identified some novel candidate genes and pathways associated with PC. Our results provide novel clues for the genetic mechanism studies of pancreatic cancer.
Highlights
Pancreatic cancer(PC) is a deadly disease, which leads to an estimated 227 000 deaths per year worldwide.[1]
After comparing the genes identified by transcriptome‐wide association study (TWAS) with the overexpressed and down‐expressed genes detected by Oncomine, we found one overlapped gene SOX4, which was overexpressed in pancreatic cancer (PC) patients
As there is no standard program for screening patients at early‐stage of PC, it is necessary to find more effective susceptibility gene for PC prevention
Summary
Pancreatic cancer(PC) is a deadly disease, which leads to an estimated 227 000 deaths per year worldwide.[1]. More than 90% of PCs originate from ductal epithelium.[2] Risk factors for this malignant disease include smoking, advanced age, family history of chronic pancreatitis, male sex, diabetes, obesity, non‐O blood group, occupational exposures, diets high in meat and low in vegetables, and probable Helicobacter pylori infection and periodontosis.[1]. The cause of PC is multifactorial, the most important risk factors are smoking and family history.Nearly 20% of pancreatic tumors are caused by smoking, and cancers from smokers suffer more genetic mutations than those from nonsmokers.[1]. Multiple genetic studies have been implemented and identified some susceptibility genes. The functional relevance of identified genes with PC was further validated by Oncomine, STRING, and CluePedia tool
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