title: GPX2 underexpression indicates poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.
abstract: OBJECTIVE
  Oxidative stress is believed to be one of the important etiologies in carcinogenesis that has not been systemically investigated in urothelial carcinoma (UC). Through data mining from a published transcriptomic database of UC of urinary bladders (UBUCs) (GSE31684), glutathione peroxidase 2 (GPX2) was identified as the most significant downregulated gene among those response to oxidative stress (GO:0006979). We therefore analyze GPX2 transcript and protein expressions and its clinicopathological significance.
  
  
  METHODS
  Real-time RT-PCR assay was used to detect GPX2 mRNA level in 20 fresh UBUC specimens. Immunohistochemistry was used to determine GPX2 protein expression in 340 urothelial carcinomas of upper tracts (UTUCs) and 295 UBUCs with mean/median follow-up of 44.7/38.9 and 30.8/23.1 months, respectively. Its expression status was further correlated with clinicopathological features and evaluated for its impact on disease-specific survival and metastasis-free survival (MeFS).
  
  
  RESULTS
  Decrease in GPX2 transcript level was associated with both higher pT and positive nodal status in 20 UBUCs (all p < 0.05). GPX2 protein underexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs (all p < 0.05). GPX2 underexpression not only predicted dismal DDS and MeFS at univariate analysis, but also implicated worse DDS (UTUC, p = 0.002; UBUC, p = 0.029) and MeFS (UTUC, p = 0.001; UBUC, p = 0.032) in multivariate analysis.
  
  
  CONCLUSIONS
  GPX2 underexpression is associated with advanced tumor status and implicated unfavorable clinical outcome of UCs, suggesting its role in tumor progression and may serve as a theranostic biomarker of UCs.
authors: Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.|Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors: I-Wei
authors: IW
authors: Chang
authors: Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.|Department of Urology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors: Victor Chia-Hsiang
authors: VC
authors: Lin
authors: Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.
authors: Chih-Hsin
authors: CH
authors: Hung
authors: Department of Urology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors: Hua-Pin
authors: HP
authors: Wang
authors: Department of Urology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors: Yung-Yao
authors: YY
authors: Lin
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
authors: Wen-Jeng
authors: WJ
authors: Wu
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chun-Nung
authors: CN
authors: Huang
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors: Ching-Chia
authors: CC
authors: Li
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Wei-Ming
authors: WM
authors: Li
authors: College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Jui-Yu
authors: JY
authors: Wu
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. angelo.p@yahoo.com.tw.|Department of Pathology, Chi Mei Foundation Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan, 701, Taiwan. angelo.p@yahoo.com.tw.|Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. angelo.p@yahoo.com.tw.|Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan. angelo.p@yahoo.com.tw.
authors: Chien-Feng
authors: CF
authors: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002681:China / Q000453:epidemiology; D018450:Disease Progression; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D018384:Oxidative Stress / Q000235:genetics; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate / Q000639:trends; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014551:Urinary Tract / Q000201:enzymology / Q000473:pathology; D014571:Urologic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000201:enzymology* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; C117436:GPX2 protein, human; D005979:Glutathione Peroxidase
keywords: GPX2; Glutathione peroxidase 2; Prognosis; Urothelial carcinoma