Genome-scale analysis to identify prognostic markers in patients with early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy

Abstract

Background

Molecular analysis is a promising source of clinically useful prognostic biomarkers. The aim of this investigation was to identify prognostic biomarkers for patients with early-stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy.

Methods

An RNA sequencing dataset of PDAC was obtained from The Cancer Genome Atlas. Survival analysis and weighted gene co-expression network analysis were used to investigate the prognostic markers of early-stage PDAC after pancreaticoduodenectomy.

Results

Using whole genome expression level screening, we identified 1,238 markers that were related to the prognosis of PDAC after pancreaticoduodenectomy, and identified 9 hub genes (ARHGAP30, HCLS1, CD96, FAM78A, ARHGAP15, SLA2, CD247, GVINP1, and IL16) using the weighted gene co-expression network analysis approach. We also constructed a signature comprising the 9 hub genes and weighted by the regression coefficient derived from a multivariate Cox proportional hazards regression model to divide patients into a high-risk group, with increased risk of death, and a low-risk group, with significantly improved overall survival (adjusted P=0.026, adjusted HR =0.513, 95% CI =0.285–0.924). The prognostic signature of the 9 genes demonstrated good performance for predicting 1-year overall survival (area under the respective receiver operating characteristic curves =0.641).

Conclusion

Our results have provided a new prospect for prognostic biomarkers of PDAC after pancreaticoduodenectomy, and may have a value in clinical application.

Keywords:

• prognostic
• pancreatic ductal adenocarcinoma
• TCGA
• WGCNA
• pancreaticoduodenectomy

Acknowledgments

This work was supported in part by the National Nature Science Foundation of China (No: 81560535, 81072321, 30760243, 30460143 and 30560133), 2009 Program for New Century Excellent Talents in University (NCET), Guangxi Nature Sciences Foundation (No: GuiKeGong 1104003A-7), and Guangxi Health Ministry Medicine Grant (Key-Scientific Research-Grant Z201018). Self-raised Scientific Research Fund of the Health and Family Planning Commission of Guangxi Zhuang Autonomous Region (Z2016318). The authors thank the contributors of TCGA for sharing the PDAC data on open access. In addition, we also would like to acknowledge the helpful comments on this paper received from our reviewers.

Disclosure

The authors report no conflicts of interest in this work.