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

Hui Wang; Ming Zhan; Ruimeng Yang; Yongheng Shi; Qiang Liu; Jian Wang

doi:10.1080/15384101.2018.1520558

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.

Authors

Hui Wang¹, Ming Zhan¹, Ruimeng Yang², Yongheng Shi³, Qiang Liu³, Jian Wang¹

Affiliations

¹ a Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai , China.
² b The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital , Shanghai Jiaotong University School of Medicine , Shanghai , China.
³ c Department of Pathology, Renji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai , China.

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

Grants and funding

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).