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. 2015 Apr 15;7(4):710-22.
eCollection 2015.

CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder

I-Wei Chang  1 , Victor Chia-Hsiang Lin  2 , Hong-Lin He  3 , Chao-Tien Hsu  3 , Ching-Chia Li  4 , Wen-Jeng Wu  5 , Chun-Nung Huang  6 , Ting-Feng Wu  7 , Chien-Feng Li  8
Affiliations

CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder

I-Wei Chang et al. Am J Transl Res. .

Abstract

Aims: Urothelial carcinoma (UC) is the most common tumor involving upper urinary tract (UTUC) and urinary bladder (UBUC) whose molecular survival determinants remains obscured. By computerizing a public transcriptomic database of UBUCs (GSE32894), we identified cell division cycle associated 5 (CDCA5) as the most significantly upregulated gene among those associated with G1-S transition of the mitotic cell cycle (GO:0000082). We therefore analyzed the clinicoptaological significance of CDCA5 expression in our well-characterized UC cohort.

Methods and results: Quantigene assay was used to detect CDCA5 transcript levels in 36 UTUCs and 30 UBUCs. We used immunohistochemistry evaluated by H-scores to determine CDCA5 protein expression in 295 UBUCs and 340 UTUCs, respectively. CDCA5 expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). For both groups of UCs, increments of CDCA5 transcript levels were associated with higher pT status, CDCA5 protein overexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses. CDCA5 overexpression was predictive for worse DSS and MeFS in univariate and multivariate analysis.

Conclusions: CDCA5 overexpression is associated with advanced clinical features of UC, suggesting its potential value as a prognostic biomarker and a novel therapeutic target.

Keywords: CDCA5; cell division cycle associated 5; upper tract; urinary bladder; urothelial carcinoma.

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Figures

Figure 1
Figure 1
Analysis of gene expression in urothelial carcinoma from a published transcriptomic dataset (GSE32894). Clustering analysis of genes focusing on the G1-S transition of the mitotic cell cycle (GO:0000082) revealed CDCA5 is the most significantly up-regulated gene associated with increments of pT status. Tissue specimens from tumors with different pT statuses are indicated on top of the heatmap, and expression levels of up-regulated and down-regulated genes are represented as a spectrum of brightness or red and green, respectively. Those unaltered in mRNA transcriptional level are coded black.
Figure 2
Figure 2
Quantitative real-time PCR (qPCR) analysis showed that CDCA5 mRNA expression was significantly increased in both UBUCs (left panel) and UTUCs (right panel) with advanced primary pT status. (p = 0.008 and p = 0.021, respectively).
Figure 3
Figure 3
CDCA5 immunostaining on representative sections of non-tumor urothelium (A), non-invasive urothelial carcinoma of low grade (B) and high grade (C) and high-grade infiltrating urothelial carcinoma (D), respectively, exhibits stepwise increased CDCA5 expression.
Figure 4
Figure 4
Kaplan-Meier plots reveal the prognostic significance of pT status and CDCA5 expression for disease-specific and metastasis-free survival of upper tract urothelial carcinoma (A-D) and urinary bladder urothelial carcinoma (E-H).
See this image and copyright information in PMC

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