Elevated expression of NFE2L3 predicts the poor prognosis of pancreatic cancer patients

Cell Cycle. 2018;17(17):2164-2174. doi: 10.1080/15384101.2018.1520558. Epub 2018 Sep 22.

Abstract

The highly malignant feature and difficulties for early diagnosis are the key reasons contributing to the poor prognosis of pancreatic cancer (PC) patients. NFE2L3 is a nuclear transcription factor, which has been reported an important biomarker of several tumors. But the role of NFE2L3 in PC remained undefined. Herein, through qPCR and immunohistochemistry, we found a significantly increased NFE2L3 in PC tissues as compared with adjacent non-tumor tissues. While reducing NFE2L3 expression suppressed the invasion abilities of PC cells, elevated NFE2L3 was found associated with lymph node metastasis (P = 0.001; HR = 3.95; 95% CI: 1.70 - 9.17) and advanced TNM stages (P < 0.001; HR = 4.06; 95% CI: 1.74 - 9.46). Consistently, data from both our two cohorts and the TCGA database revealed that higher NFE2L3 PC carriers had worse outcomes than those lower NFE2L3 expressers. Lastly, we confirmed the regulatory role of NFE2L3 on VEGFA, an important player involved in tumor angiogenesis. Collectively, our investigations suggested the oncogenic role of NFE2L3 in PC development and provided the rational for future adding NFE2L3 for the risk assessment of PC patients.

Abbreviations: NFE2L3: NF-E2-related factor 3; UHMK1: U2AF homology motif kinase 1; VEGFA: vascular endothelial growth factor A; GEO: gene expression omnibus; TCGA: The Cancer Genome Atlas; HPDE: human pancreas duct cells; OS: overall survival; IHC: immunohistochemistry; FFPE: formalin-fixed and paraffin-embedded; SEM: standard error of mean.

Keywords: NFE2L3; Pancreatic cancer; VEGFA; biomarker; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Biomarkers, Tumor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunohistochemistry / methods
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Biomarkers, Tumor
  • NFE2L3 protein, human
  • Vascular Endothelial Growth Factor A

Grant support

This work was supported by the Foundation of Shanghai Shen Kang Hospital Development Center (No. 16CR2002A and 16CR3028A), National Science Foundation of China (No. 81472240 and 81773184), and Shanghai Outstanding Academic Leaders Plan (2016, JW).