Upregulation of Cartilage Oligomeric Matrix Protein Predicts Poor Prognosis in Urothelial Carcinoma

Abstract

Yu-Hsuan Kuo,1,2 Hong-Yue Lai,3 Ti-Chun Chan,3,4 Chung-Hsi Hsing,3,5 Steven K Huang,6,7 Kun-Lin Hsieh,6 Tzu-Ju Chen,8,9 Wan-Shan Li,9,10 Jhih-Cheng Lu,11,* Chien-Feng Li3,4,* 1Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, 71004, Taiwan; 2College of Pharmacy and Science, Chia Nan University, Tainan, 71710, Taiwan; 3Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan; 4National Institute of Cancer Research, National Health Research Institutes, Tainan, 704, Taiwan; 5Department of Anesthesiology, Chi Mei Medical Center, Tainan, 710, Taiwan; 6Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan; 7Department of Medical Science Industries, College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan; 8Department of Clinical Pathology, Chi Mei Medical Center, Tainan, 710, Taiwan; 9Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan; 10Department of Pathology, Chi Mei Medical Center, Tainan, 710, Taiwan; 11Division of Urology, Department of Surgery, Chi Mei Medical Center, Liouying, 736, Taiwan*These authors contributed equally to this workCorrespondence: Chien-Feng Li, Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan, Tel [phone], Fax [phone], Email [email protected]: Cartilage oligomeric matrix protein (COMP) is known as a large pentameric glycoprotein, which interacts with various extracellular matrix proteins in tissues. COMP has been reported to play a role in multiple connective tissue disorders. Recently, elevated COMP levels have been found to be associated with increased tumor size, metastases, faster recurrence of cancer, and overall poorer survival in several cancers. However, the clinical importance of COMP in urothelial carcinoma remains unclear. We investigated the association between COMP expression and clinical outcomes in urothelial carcinoma.Patients and Methods: In this retrospective study, we collected urothelial carcinoma (UC) tissue from 340 upper urinary tract UC (UTUC) patients and 295 urinary bladder UC (UBUC) patients. Pearson’s chi-square test, Kaplan–Meier analysis, and the multivariate Cox proportional hazards model was used to examine the relationship between COMP expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MFS) and disease-specific survival (DSS).Results: A total of 295 UBUC patients and 340 UTUC patients were recruited. The COMP mRNA level was significantly higher among invasive tumors (pT2–pT4) than in noninvasive tumors (pTa-T1) in UBUC groups (P < 0.01). COMP overexpression was associated with advanced T stage, nodal metastases, vascular invasion, perineural invasion, high histological grade, and high mitotic rate in both UBUC and UTUC cohorts. COMP overexpression was predictive of shorter DSS (hazard ratio [HR] in UBUC, 3.986, P < 0.001; in UTUC, 2.283, P = 0.027] and MFS (HR in UBUC, 6.813, P < 0.001; in UTUC, 4.070, P < 0.001). Kaplan–Meier analysis demonstrated high COMP expression associated with poor DSS and MFS in UTUC and UBUC groups (all P < 0.0001).Conclusion: COMP overexpression was linked to poor clinical prognosis and poor pathological features in UC. These results suggest COMP as a biomarker for UC.Keywords: cartilage oligomeric matrix protein, urothelial carcinoma, extracellular matrix structure constituent, prognosis

Keywords

• cartilage oligomeric matrix protein
• urothelial carcinoma
• extracellular matrix structure constituent
• prognosis