GPX2 underexpression indicates poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder
0301 basic medicine
Carcinoma, Transitional Cell
China
Glutathione Peroxidase
Urologic Neoplasms
Prognosis
Real-Time Polymerase Chain Reaction
Immunohistochemistry
Disease-Free Survival
3. Good health
Gene Expression Regulation, Neoplastic
Survival Rate
Oxidative Stress
03 medical and health sciences
Urinary Bladder Neoplasms
Biomarkers, Tumor
Disease Progression
Humans
RNA, Neoplasm
Urothelium
Urinary Tract
Neoplasm Staging
DOI:
10.1007/s00345-015-1522-7
Publication Date:
2015-03-26T18:55:41Z
AUTHORS (11)
ABSTRACT
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.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).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.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.
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