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. 2016 Jun 30;7(11):1396-405.
doi: 10.7150/jca.15339. eCollection 2016.

Complement Component 1, s Subcomponent Overexpression is an Independent Poor Prognostic Indicator in Patients with Urothelial Carcinomas of the Upper Urinary Tract and Urinary Bladder

I-Wei Chang  1 , Victor Chia-Hsiang Lin  2 , Wen-Jen Wu  3 , Peir-In Liang  4 , Wei-Ming Li  5 , Bi-Wen Yeh  5 , Hong-Lin He  6 , Alex Chien-Hwa Liao  7 , Ti-Chun Chan  8 , Chien-Feng Li  9
Affiliations

Complement Component 1, s Subcomponent Overexpression is an Independent Poor Prognostic Indicator in Patients with Urothelial Carcinomas of the Upper Urinary Tract and Urinary Bladder

I-Wei Chang et al. J Cancer. .

Abstract

Purpose: Urothelial carcinoma of the urinary bladder and upper tract is prevalent. By subjecting a documented transcriptome data set of urothelial carcinoma of bladder (GSE31684) to data mining and focusing on genes linked to peptidase activity (GO:0008233), we recognized C1S as the most significantly upregulated gene related to an advanced tumor status and metastasis. We subsequently analyzed the association of both C1S mRNA and its encoded protein expression with the clinical and pathological significance.

Materials and methods: We used real-time reverse transcription polymerase chain reaction to detect C1S transcription levels in 20 cases each of urothelial carcinoma of bladder and upper tract. An immunohistochemical stain was conducted to determine C1s protein expression levels in patients with urothelial carcinoma of upper tract (n = 340) and urinary bladder (n = 295). Furthermore, we examined the correlation of C1s expression with clinicopathological characteristics, disease-specific survival, and metastasis-free survival.

Results: C1S transcription levels were significantly high in patients with advanced-stage tumors of both groups (all P < .05). Immunohistochemical analysis revealed that C1s expression levels were significantly associated with adverse clinicopathological parameters in both groups of urothelial carcinoma (all P < .05). C1s overexpression predicted poor disease-specific and metastasis-free survival rates for both urothelial carcinoma groups in the univariate analysis, and it was also an independent prognostic factor in the multivariate analysis (all P < .05).

Conclusions: C1s may play a pivotal role in urothelial carcinoma progress and can represent a vital prognostic marker and a promising new therapeutic target in urothelial carcinoma.

Keywords: C1S gene; Complement component 1s; Prognosis.; Urothelial carcinoma.

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Conflict of interest statement

Competing Interests: The authors declare no potential conflicts of interest.

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 peptidase activity (GO:0008233) revealed that C1S 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
Quantitative real-time reverse-transcription polymerase chain reaction analysis. This analysis revealed a significantly higher C1S transcription level in both urothelial carcinomas of the upper urinary tract (left panel) and urinary bladder (right panel), with a more advanced primary tumor aggressiveness, compared with non-invasive and superficially invasive tumors (pTa-pT1) and deeply invasive ones (pT2-pT4), respectively (all P < .005).
Figure 3
Figure 3
C1s immunostain on representative sections revealed a stepwise increment in C1s immunoreactivity from the nontumoral urothelial epithelium (inlet) and non-invasive papillary urothelial carcinomas (A) to non-muscle invasive (pT1) (B), and muscle invasive (pT2-pT4) urothelial carcinomas (C).
Figure 4
Figure 4
Kaplan-Meier plots revealed the significant prognostic value of C1s expression for disease-specific survival (DSS) and metastasis-free survival (MeFS) rates in the UCUT (A and B for DSS and MeFS, respectively) and UCUB (C and D for DSS and MeFS, respectively) groups (all P < .0001).
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