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

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.

Elevated THBS2, COL1A2, and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis

“…While Sun et al used 14 pairs of gastric tumor tissues and adjacent normal tissues in their study, we used a larger number of tissues, which makes our results more convincing. Other than gastric cancer, THBS2 has also been identified as a prognostic indicator for patients with urothelial carcinomas of the upper urinary tract and bladder [21]. Consistent with our study, in urothelial cancer, THBS2 overexpression was linked to poor prognosis, namely, disease-specific survival and metastasis-free survival.…”

Downregulation of RNF128 Predicts Progression and Poor Prognosis in Patients with Urothelial Carcinoma of the Upper Tract and Urinary Bladder

“…More than 90% of UCs arise in the urinary bladder, and only 5% to 10% of all UCs develop in the upper urinary tract 1-3. Although growing evidence has suggested that UBUC and upper urinary tract UC (UTUC) may share several biologically unique features, there are certain significant similarities between both types of UCs 4-9. Additionally, it was reported that there was a 30-50% risk of bladder recurrence within 5 years for patients with UTUC receiving radical nephroureterectomy and a 2-6% risk of developing subsequent UTUC after initial diagnosis with UBUC 10-11.…”

MicroRNA‑203a‑3p is a candidate tumor suppressor that targets thrombospondin 2 in colorectal carcinoma

“…THBS2, secreted by stromal fibroblasts, endothelial cells and immune cells, and belongs to the THBS family of proteins, was identified in 1991 and its sequence was analyzed in 1997 (24,25). Subsequently, it was found to be associated with various cancer types (22,(26)(27)(28)(29)(30). The aim of the present study was to investigate the expression of THBS2 in CRC tissues, and determine its link with the overall survival (OS) and disease-free survival (DFS) in patients with CRC.…”