title: Aberrant expression of peroxiredoxin 1 and its clinical implications in liver cancer.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Bi
authors.affiliation: 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.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Xiao-Hang
authors.initials: XH
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D003546:Cysteine Endopeptidases / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism*; D012737:Sex Factors; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human
keywords: Liver cancer; Peroxiredoxin 1; Post-translational modification; Prognostic factor; SUMOylation