Research Paper Volume 12, Issue 23 pp 24228—24241

The value of a metabolic reprogramming-related gene signature for pancreatic adenocarcinoma prognosis prediction

Zhen Tan1,2,3,4, *, , Yubin Lei1,2,3,4, *, , Jin Xu1,2,3,4, *, , Si Shi1,2,3,4, , Jie Hua1,2,3,4, , Bo Zhang1,2,3,4, , Qingcai Meng1,2,3,4, , Jiang Liu1,2,3,4, , Yiyin Zhang1,2,3,4, , Miaoyan Wei1,2,3,4, , Xianjun Yu1,2,3,4, , Chen Liang1,2,3,4, ,

  • 1 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
  • 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • 3 Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
  • 4 Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
* Equal contribution

Received: June 3, 2020       Accepted: September 9, 2020       Published: November 20, 2020
How to Cite

Copyright: © 2020 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. Extensive enhancement of glycolysis and reprogramming of lipid metabolism are both associated with the development and progression of PDAC. Previous studies have suggested that various gene signatures could convey prognostic information about PDAC. However, the use of these signatures has some limitations, perhaps because of a lack of knowledge regarding the genetic and energy supply backgrounds of PDAC. Therefore, we conducted multi-mRNA analysis based on metabolic reprogramming to identify novel signatures for accurate prognosis prediction in PDAC patients. In this study, a three-gene signature comprising MET, ENO3 and CD36 was established to predict the overall survival of PDAC patients. The three-gene signature could divide patients into high- and low-risk groups by disparities in overall survival verified by log-rank test in two independent validation cohorts and could differentiate tumors from normal tissues with excellent accuracy in four Gene Expression Omnibus (GEO) cohorts. We also found a positive correlation between the risk score of the gene signature and inherited germline mutations in PDAC predisposition genes. A glycolysis and lipid metabolism-based gene nomogram and corresponding calibration curves showed significant performance for survival prediction in the TCGA-PDAC dataset. The high-risk designation was closely connected with oncological signatures and multiple aggressiveness-related pathways, as determined by gene set enrichment analysis (GSEA). In summary, our study developed a three-gene signature and established a prognostic nomogram that objectively predicted overall survival in PDAC. The findings could provide a reference for the prediction of overall survival and could aid in individualized management for PDAC patients.


AUC: area under the curve; DEG: differentially expressed genes; FAs: fatty acids; FUSCC: Fudan University Shanghai Cancer Center; FDR: false discovery rate; GEO: Gene Expression Omnibus; GSEA: gene set enrichment analysis; ICGC: International Cancer Genome Consortium; LASSO: least absolute shrinkage and selection operator; MSigDB: Molecular Signatures Database; OS: overall survival; PDAC: pancreatic ductal adenocarcinoma; TCGA: The Cancer Genome Atlas.