Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2015; 21(38): 10840-10852
Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10840
Aberrant expression of peroxiredoxin 1 and its clinical implications in liver cancer
Yu-Lin Sun, Jian-Qiang Cai, Fang Liu, Xin-Yu Bi, Lan-Ping Zhou, Xiao-Hang Zhao
Yu-Lin Sun, Fang Liu, Lan-Ping Zhou, Xiao-Hang Zhao, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Jian-Qiang Cai, Xin-Yu Bi, Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China
Author contributions: Sun YL performed the majority of the work, data analysis, and wrote the manuscript; Liu F and Zhou LP assisted in the experiments; Bi XY collected the clinical specimens; Zhao XH and Cai JQ supervised this work; Sun YL, Cai JQ, and Zhao XH designed the study.
Supported by State Key Project for Infectious Diseases, No. 2013ZX10002009 and No. 2012ZX10002-017; State Key Project for Basic Research, No. 2014CBA02001 and No. 2014CBA02002; National High-tech R and D Program, No. 2012AA020206; and Natural Science Foundation of China, No. 81071789 and No. 81321091.
Institutional review board statement: All routine colonic biopsy specimens and blood samples from the patients were taken after informed consent and ethical permission was obtained for participation in the study.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiao-Hang Zhao, MD, PhD, Professor, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17, Chaoyang District, Beijing 100021, China. zhaoxh@cicams.ac.cn
Telephone: +86-10-67709015 Fax: +86-10-87778360
Received: April 21, 2015
Peer-review started: April 22, 2015
First decision: June 19, 2015
Revised: July 2, 2015
Accepted: August 31, 2015
Article in press: August 31, 2015
Published online: October 14, 2015
Processing time: 175 Days and 20.1 Hours
Abstract

AIM: To investigate the expression characteristics of peroxiredoxin 1 (PRDX1) mRNA and protein in liver cancer cell lines and tissues.

METHODS: The RNA sequencing data from 374 patients with liver cancer were obtained from The Cancer Genome Atlas. The expression and clinical characteristics of PRDX1 mRNA were analyzed in this dataset. The Kaplan-Meier and Cox regression survival analysis was performed to determine the relationship between PRDX1 levels and patient survival. Subcellular fractionation and Western blotting were used to demonstrate the expression of PRDX1 protein in six liver cancer cell lines and 29 paired fresh tissue specimens. After bioinformatics prediction, a putative post-translational modification form of PRDX1 was observed using immunofluorescence under confocal microscopy and immunoprecipitation analysis in liver cancer cells.

RESULTS: The mRNA of PRDX1 gene was upregulated about 1.3-fold in tumor tissue compared with the adjacent non-tumor control (P = 0.005). Its abundance was significantly higher in men than women (P < 0.001). High levels of PRDX1 mRNA were associated with a shorter overall survival time (P = 0.04) but not with recurrence-free survival. The Cox regression analysis demonstrated that patients with high PRDX1 mRNA showed about 1.9-fold increase of risk for death (P = 0.03). In liver cancer cells, PRDX1 protein was strongly expressed with multiple different bands. PRDX1 in the cytosol fraction existed near the theoretical molecular weight, whereas two higher molecular weight bands were present in the membrane/organelle and nuclear fractions. Importantly, the theoretical PRDX1 band was increased, whereas the high molecular weight form was decreased in tumor tissues. Subsequent experiments revealed that the high molecular weight bands of PRDX1 might result from the post-translational modification by small ubiquitin-like modifier-1 (SUMO1).

CONCLUSION: PRDX1 was overexpressed in the tumor tissues of liver cancer and served as an independent poor prognostic factor for overall survival. PRDX1 can be modified by SUMO to play specific roles in hepatocarcinogenesis.

Keywords: Peroxiredoxin 1; Liver cancer; Prognostic factor; Post-translational modification; SUMOylation

Core tip: Peroxiredoxin 1 (PRDX1) is an antioxidant enzyme, and, therefore, it is considered a tumor suppressor gene. However, only recently has various data revealed that PRDX1 not only functions in peroxide detoxification but also in tumorigenesis. Here, we found that PRDX1 was overexpressed in liver cancer at the transcriptional level, and it was an independent unfavorable prognostic factor for overall survival. In liver cancer cells, PRDX1 is post-translationally modified by small ubiquitin-like modifier. The downregulation of sumoylated PRDX1 in tumors might participate in hepatocarcinogenesis. PRDX1 represents both a prognostic biomarker and therapeutic target for liver cancer.