J Cancer 2016; 7(11):1396-1405. doi:10.7150/jca.15339

Research Paper

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 Chang1,2, Victor Chia-Hsiang Lin2,3, Wen-Jen Wu4,5,6,7,8, Peir-In Liang9, Wei-Ming Li5,6,7,8, Bi-Wen Yeh5,6,7,8, Hong-Lin He1, Alex Chien-Hwa Liao10,✉, Ti-Chun Chan11, Chien-Feng Li11,12,13,14,✉

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

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, Urothelial carcinoma, Prognosis.

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How to cite this article:
Chang IW, Lin VCH, Wu WJ, Liang PI, Li WM, Yeh BW, He HL, Liao ACH, Chan TC, Li CF. 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. J Cancer 2016; 7(11):1396-1405. doi:10.7150/jca.15339. Available from http://www.jcancer.org/v07p1396.htm