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Research Paper|Volume 11, Issue 3|pp 885—897

Three hypomethylated genes were associated with poor overall survival in pancreatic cancer patients

Huiming Chen1,2, Yan Kong3, Qing Yao1, Xing Zhang1, Yunong Fu1, Jia Li4, Chang Liu1, Zheng Wang1
  • 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
  • 2Department of General Surgery, Shaanxi Provincial Rehabilitation Hospital,Xi’an 710065, Shaanxi, China
  • 3Department of Clinical Laboratory, Liaocheng People’s Hospital, Taishan Medical College, Liaocheng 252000, Shandong, China
  • 4Department of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
Received: December 2, 2018Accepted: January 15, 2019Published: February 1, 2019
https://doi.org/10.18632/aging.101785

Copyright: © 2019 Chen 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.

Abstract

Pancreatic cancer (PC) is a highly malignant cancer with poor prognosis and high mortality. Aberrant DNA methylation plays a critical role in the occurrence, progression and prognosis of malignant tumors. In this study, we employed multiple datasets from APGI, TCGA and GEO to perform Multi-Omics analysis, including DNA methylation and expression profiling analysis. Three differentially expressed genes (SULT1E1, IGF2BP3, MAP4K4) with altered status of DNA methylation were identified and then enrolled into prognostic risk score model using LASSO regression. Univariate cox regression analysis indicated that high risk score was significantly associated with poor prognosis. Multivariate cox regression analysis proved the risk score was an independent prognostic factor for PC. In addition, time-dependent ROC curves indicated good performance of our model in predicting the 1-, 3- and 5-year survival of PC patients. Besides, stratified survival analysis revealed that the risk score model had greater prognostic value for patients of late stage with T3/T4 and N+. Pathway enrichment analysis suggested that these three genes might promote tumor progression by affecting signaling by Rho GTPases and chromosome segregation. In summary, three hypomethylated gene signature were significantly associated with patients’ overall survival, which might serve as potential prognostic biomarkers for PC patients.