Dataset Information

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

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.

SUBMITTER: Wang H

PROVIDER: S-EPMC6226237 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Wang Hui H Zhan Ming M Yang Ruimeng R Shi Yongheng Y Liu Qiang Q Wang Jian J

Cell cycle (Georgetown, Tex.) 20180922 17

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 suppr ...[more]

PMID: 30196752

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is a growing cause of cancer-related mortality worldwide. Kallikrein-related peptidase 8 (KLK8) has potential clinical values in many cancers. However, the clinicopathological significances of KLK8 in PDAC remain unknown. We explored the relationship of KLK8 to clinicopathological features of PDAC based on public databases. KLK8 expression was examined in human PDAC tissues. Cell proliferation and apoptosis were evaluated in KLK8-overexpressed human pancreatic cancer cell lines Mia-paca-2 and Panc-1. The related signaling pathways of KLK8 involved in pancreatic cancer progression were analyzed by gene set enrichment analysis (GSEA) and further verified in in vitro studies. We found that KLK8 was up-regulated in tumor tissues in the TCGA-PAAD cohort, and was an independent prognostic factor for both overall survival and disease-free survival of PDAC. KLK8 mRNA and protein expressions were increased in PDAC tissues compared with para-cancerous pancreas. KLK8 overexpression exerted pro-proliferation and anti-apoptotic functions in Mia-paca-2 and Panc-1 cells. GSEA analysis showed that KLK8 was positively associated with PI3K-Akt-mTOR and Notch pathways. KLK8-induced pro-proliferation and anti-apoptotic effects in Mia-paca-2 and Panc-1 cells were attenuated by inhibitors for PI3K, Akt, and mTOR, but not by inhibitor for Notch. Furthermore, overexpression of KLK8 in Mia-paca-2 and Panc-1 cells significantly increased epidermal growth factor (EGF) levels in the culture media. EGF receptor (EGFR) inhibitor could block KLK8-induced activation of PI3K/Akt/mTOR pathway and attenuate pro-proliferation and anti-apoptotic of KLK8 in Mia-paca-2 and Panc-1 cells. In conclusion, KLK8 overexpression exerts pro-proliferation and anti-apoptotic functions in pancreatic cancer cells via EGF signaling-dependent activation of PI3K/Akt/mTOR pathway. Upregulated KLK8 in PDAC predicts poor prognosis and may be a potential therapeutic target for PDAC.

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

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

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