MiR-146a、MMP-2 與 MMP-9 基因多型性作為台灣泌尿上皮癌風險預測生物標記之研究

王柏仁^1,2,4、廖丞晞^1,2,3、王韻琪^3,4、張文馨^3,4、蔡佳紋^3,4、包大靝^3,4

1國軍臺中總醫院泌尿外科，2國防醫學大學，

3中國醫藥大學附設醫院泰瑞法克斯癌症研究實驗室，

4中國醫藥大學生物醫學研究所

Genetic Polymorphisms of miR-146a, MMP-2, and MMP-9 as Predictive Biomarkers for Urothelial Carcinoma Risk in Taiwan

Bo-Ren, Wang^1,2、Cheng-Hsi Liao^1,2、Yun-Chi Wang^3,4、Wen-Shin Chang^3,4、Chia-Wen Tsai^3,4、Da-Tian Bau^3,4

¹Division of Urology, Department of surgery, Taichung Armed Forces General Hospital

²National Defense Medical University ³Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital ⁴Graduate Institute of Biomedical Sciences, China Medical University

Purpose: Urothelial carcinoma (UC), including bladder cancer (BLCA) and upper tract urothelial carcinoma (UTUC), is highly prevalent in Taiwan. Genetic polymorphisms in microRNAs and matrix metalloproteinases (MMPs) may contribute to carcinogenesis through regulation of gene expression, extracellular matrix remodeling, and tumor invasion.

Materials and Methods: We conducted hospital-based case–control studies in Taiwanese populations. For BLCA, 375 patients and 375 controls were genotyped for miR-146a rs2910164 and miR-196a rs11614913 polymorphisms. For UTUC, 218 patients and 580 controls were analyzed for MMP-2 (rs243865, rs2285053) and MMP-9 (rs3918242) polymorphisms. Genotyping was performed using PCR-RFLP. Serum miR-146a levels and MMP-2/MMP-9 mRNA and protein expression were evaluated to explore genotype–phenotype correlations.

Results: The miR-146a rs2910164 GG genotype was significantly associated with increased BLCA risk (OR = 2.17), accompanied by elevated circulating miR-146a expression.

In UTUC, MMP-2 rs2285053 TT genotype (OR = 2.20) and MMP-9 rs3918242 CT/TT genotypes (OR = 1.51–2.92) were significantly associated with increased cancer susceptibility.

Furthermore, risk genotypes of MMP-2 and MMP-9 correlated with higher mRNA and protein expression levels, suggesting functional relevance in tumor progression.

Conclusions: MiR-146a, MMP-2, and MMP-9 polymorphisms are significantly associated with urothelial carcinoma susceptibility in Taiwan. These genetic variants demonstrate consistent genotype–phenotype correlations and may serve as potential non-invasive biomarkers for risk stratification and early detection of UC.