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. 2016 Jul 8;7(11):1541-9.
doi: 10.7150/jca.15696. eCollection 2016.

Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders

I-Wei Chang  1 , Chien-Feng Li  2 , Victor Chia-Hsiang Lin  3 , Hong-Lin He  4 , Per-In Liang  5 , Wen-Jeng Wu  6 , Ching-Chia Li  6 , Chun-Nung Huang  7
Affiliations

Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders

I-Wei Chang et al. J Cancer. .

Abstract

Purpose: Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By data mining a published dataset of UC of bladder (UCB) transcriptome (GSE31684) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that THBS2 was the most significantly upregulated gene among those related to structural molecule activity (GO:0005198). Therefore, we evaluated the clinical significance and prognostic impact of thrombospondin-2 (THBS2) protein, A.K.A. TSP2, which encoded by THBS2 gene.

Materials and methods: THBS2 immunostaining was performed in 340 UCs of upper urinary tract (UC-UUTs) and 295 UCBs; subsequently, both groups were dichotomized into high- and low-expression subgroups. Moreover, statistical analyses were performed to correlate the association between THBS2 expression and clinicopathological parameters with two survival indexes: disease-specific survival (DSS) and metastasis-free survival (MeFS).

Results: High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001). In addition, THBS2 overexpression was linked to adverse DSS and MeFS in univariate analyses and served as an independent prognosticator indicating poor outcomes in both groups in multivariate analyses.

Conclusion: THBS2 may play a crucial role in UC progression and may be a novel prognostic marker. Additional investigations to elucidate the molecular pathway are necessary for developing potential THBS2-targeted therapies for UCs.

Keywords: THBS2; TSP2; prognosis; thrombospondin-2; urothelial carcinoma..

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Conflict of interest statement

Competing Interests: No conflicts of interest to be declared.

Figures

Figure 1
Figure 1
Analysis of gene expression in urothelial carcinoma of the urinary bladder by using a published transcriptome data set (GSE31684). Conducting a clustering analysis of genes by focusing on structural molecule activity (GO:0005198) revealed that THBS2 was one of the most significantly upregulated genes associated with a more advanced pT status and metastatic disease. Tissue specimens from cancers with distinct pT statuses are illustrated at the top of the heat map, and the expression levels of upregulated and downregulated genes are represented as a continuum of brightness of red or green, respectively. Specimens with unaltered mRNA expression are in black.
Figure 2
Figure 2
THBS2 immunostain on representative tissue sections revealed a stepwise increase of THBS2 immunoreactivity from the normal urothelial epithelium (A) to noninvasive papillary (pTa) (B), superficially infiltrating (pT1) (C), and muscle invasive (pT2-pT4) urothelial carcinomas (D).
Figure 3
Figure 3
Kaplan-Meier plots demonstrated the extremely significant prognostic value of THBS2 expression for disease-specific survival (DSS) and metastasis-free survival (MeFS) rates in the UC-UUT (A and B for DSS and MeFS, respectively) and UCB (C and D for DSS and MeFS, respectively) groups (all P < .0001).
See this image and copyright information in PMC

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