High MT2A Expression Predicts Worse Prognosis in Patients with Urothelial Carcinoma

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Title:	High MT2A Expression Predicts Worse Prognosis in Patients with Urothelial Carcinoma
Authors:	Li, Wei-Ming Ke, Hung-Lung Kuo, Yu-Hsuan Lai, Hong-Yue Chan, Ti-Chun Hsing, Chung-Hsi Hsieh, Kun-Lin Li, Wan-Shan Chen, Tzu-Ju Wei, Yu-Ching Wu, Wen-Jeng Huang, Steven K. Li, Chien-Feng
Contributors:	Kaohsiung Medical University Kaohsiung Medical University Hospital Kaohsiung Municipal Ta-Tung Hospital Chi Mei Hospital Chia Nan University of Pharmacy & Science National Health Research Institutes - Taiwan Chung Hua University Kaohsiung Municipal Ta-Tung Hospital Chang Jung Christian University
Keywords:	upper urinary-tract metallothionein 2a bladder-cancer complement cells indicator risk
Date:	2022
Issue Date:	2023-12-11 14:04:12 (UTC+8)
Publisher:	KARGER
Abstract:	Introduction: Dysregulation of metal ion homeostasis is associated with urothelial carcinogenesis. From a published urinary bladder urothelial carcinoma (UBUC) transcriptome, we identified metallothionein 2A (MT2A) as the most significantly upregulated gene implicated in cancer progression among metal ion binding-related genes. Therefore, we analyzed the association between MT2A expression and clinical significance in our well-characterized cohort of patients with upper tract urothelial carcinoma (UTUC) and UBUC. Methods: We retrospectively reviewed the clinicopathological characteristics of 295 and 340 patients with UBUC and UTUC, respectively. MT2A expression was assessed using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. We further correlated MT2A expression with clinicopathological factors, disease-specific survival (DSS) and metastasis-free survival (MFS) using the Pearson's chi(2) test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model. Results: High MT2A expression was significantly associated with aggressive pathological features including high tumor stage, lymph node metastasis, high tumor grade, vascular invasion, and perineural invasion. In the Kaplan-Meier analysis, high MT2A expression was significantly correlated with poor DSS (p < 0.0001) and MFS (p < 0.0001); in the multivariate analysis, it was an independent predictor of CSS (p < 0.001) and MFS (p = 0.001). Gene coexpression analysis demonstrated that MT2A overexpression promotes UC progression through complement activation. Conclusion: High MT2A expression correlated with aggressive UC features and was an independent predictor of cancer metastasis and patient survival, suggesting its role in risk stratification and decision-making in patients with UTUC and UBUC.
Relation:	ONCOLOGY, v.100, n.9, pp.485–497
Appears in Collections:	[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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