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

Aging (Albany NY). 2019 Feb 1;11(3):885-897. doi: 10.18632/aging.101785.

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.

Keywords: DNA methylation; IGF2BP3; MAP4K4; SULT1E1; pancreatic cancer; prognostic model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Methylation*
  • Gene Expression Profiling
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Protein Serine-Threonine Kinases / genetics*
  • RNA-Binding Proteins / genetics*
  • Risk Assessment
  • Sulfotransferases / genetics*

Substances

  • IGF2BP3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • RNA-Binding Proteins
  • MAP4K4 protein, human
  • Protein Serine-Threonine Kinases
  • Sulfotransferases
  • estrone sulfotransferase