SERP1 is a novel marker of poor prognosis in pancreatic ductal adenocarcinoma patients via anti-apoptosis and regulating SRPRB/NF-κB axis

Ma,Qiang; Wu,Xiuxiu; Wu,Jing; Liang,Zhiyong; Liu,Tonghua

doi:10.3892/ijo.2017.4111

SERP1 is a novel marker of poor prognosis in pancreatic ductal adenocarcinoma patients via anti-apoptosis and regulating SRPRB/NF-κB axis

Authors:
- Qiang Ma
- Xiuxiu Wu
- Jing Wu
- Zhiyong Liang
- Tonghua Liu
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Affiliations: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, Department of Medical Imaging, Beijing Huairou Hospital, University of Chinese Academy of Science, Beijing 101400, P.R. China
Published online on: August 31, 2017 https://doi.org/10.3892/ijo.2017.4111
Pages: 1104-1114
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Stress associated endoplasmic reticulum protein 1 (SERP1), can cause accumulation of unfolded proteins in ER stress. However, studies on the role of SERP1 in pancreatic ductal adenocarcinoma (PDAC) are still incomplete. The present study aimed at identifying whether SERP1 acts as a potential novel prognostic marker of PDAC, and analyzed its possible mechanism. GEO database analysis showed SERP1 was significantly upregulated in PDAC tissues, and strongly associated with advanced clinical stage of PDAC patients from TCGA database. Univariate and multivariate Cox regression analysis further revealed SERP1 high expression was an independent factor for the prognosis of PDAC. Gene set enrichment analysis (GSEA) revealed that SERP1 was mainly involved in regulating cell apoptosis and nuclear factor-κB (NF-κB) signaling pathway, and downregulated SERP1 significantly promoted PANC-1 cell apoptosis. To further explore its possible mechanism, protein-protein interaction (PPI) and gene ontology (GO) analysis showed the functions of proteins interacting with SERP1 were mainly enriched in regulating cell apoptosis, and SRP receptor β subunit (SRPRB) was the core of the whole PPI network. The expression of SERP1 was negatively correlated with SRPRB expression. In vitro, downregulated SERP1 significantly increased SRPRB expression. Furthermore, upregulated SRPRB could increase cell apoptosis rate and decreased the expression level of NF-κB and the phosphorylation NF-κB. The above results indicated that SERP1 as a potential novel prognostic marker of PDAC probably via regulating cell apoptosis and NF-κB activation, which may be associated with SRPRB.

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