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GPX2 underexpression indicates poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

Authors :
Chang IW
Lin VC
Hung CH
Wang HP
Lin YY
Wu WJ
Huang CN
Li CC
Li WM
Wu JY
Li CF
Source :
World journal of urology [World J Urol] 2015 Nov; Vol. 33 (11), pp. 1777-89. Date of Electronic Publication: 2015 Mar 27.
Publication Year :
2015

Abstract

Purpose: 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.<br />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).<br />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.<br />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.

Details

Language :
English
ISSN :
1433-8726
Volume :
33
Issue :
11
Database :
MEDLINE
Journal :
World journal of urology
Publication Type :
Academic Journal
Accession number :
25813210
Full Text :
https://doi.org/10.1007/s00345-015-1522-7