J Cancer 2016; 7(11):1541-1549. doi:10.7150/jca.15696

Research Paper

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

I-Wei Chang1,2, Chien-Feng Li3,4,5,6, Victor Chia-Hsiang Lin2,7, Hong-Lin He1, Per-In Liang8, Wen-Jeng Wu9,10,11, Ching-Chia Li9,10,11, Chun-Nung Huang9,10✉

1. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan;
2. School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan;
3. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan;
4. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;
5. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
6. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan;
7. Department of Urology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan;
8. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan;
9. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
10. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;
11. Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.

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: prognosis, THBS2, thrombospondin-2, TSP2, urothelial carcinoma.

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How to cite this article:
Chang IW, Li CF, Lin VCH, He HL, Liang PI, Wu WJ, Li CC, Huang CN. Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders. J Cancer 2016; 7(11):1541-1549. doi:10.7150/jca.15696. Available from http://www.jcancer.org/v07p1541.htm