Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer

Chun-Yu Hsieh, Chia-Yen Lin, Shian-Shiang Wang, Ying-Erh Chou, Ming-Hsien Chien, Yu-Ching Wen, Ming-Ju Hsieh () and Shun-Fa Yang ()
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Chun-Yu Hsieh: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
Chia-Yen Lin: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
Shian-Shiang Wang: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 407, Taiwan
Ying-Erh Chou: School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
Ming-Hsien Chien: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Yu-Ching Wen: Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan
Ming-Ju Hsieh: Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan
Shun-Fa Yang: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan

IJERPH, 2022, vol. 20, issue 1, 1-11

Abstract: The tissue inhibitors of metalloproteinases-3 (TIMP3) are not only endogenous regulators of matrix metalloproteinases (MMPs), but also induce apoptosis and inhibit endothelial cell migration and angiogenesis. The focus of this study was to investigate the relationship between TIMP3 genetic polymorphisms and biochemical recurrence and clinicopathological features of prostate cancer. The TIMP3 rs9619311, rs9862, and rs11547635 genetic polymorphisms were analyzed by real-time polymerase chain reaction to determine their genotypic distributions in 579 patients with prostate cancer. This study found that individuals with the TIMP3 rs9619311 TC or TC + CC genotypes have a significantly higher risk of biochemical recurrence of prostate cancer ( p = 0.036 and 0.033, respectively). Moreover, in the multivariate analysis, our results showed that pathologic Gleason grade, pathologic T stage, seminal vesicle invasion, lymphovascular invasion, and TIMP3 rs9619311 were associated with increased odds of biochemical recurrence. Patients with a PSA concentration under 7 ng/mL that were found to have the TIMP3 rs9619311 genetic polymorphism were associated with Gleason total score upgrade ( p = 0.012) and grade group upgrade ( p = 0.023). Compared with the CC homozygous, the TIMP3 rs9862 CT + TT polymorphic variant was found to be associated with clinically advanced tumor stage ( p = 0.030) and Gleason total score upgrade ( p = 0.002) in prostate cancer patients. In conclusion, the results of our study demonstrated that the TIMP3 rs9619311 genetic polymorphism was significantly associated with susceptibility to biochemical recurrence of prostate cancer. TIMP3 genetic polymorphisms, especially rs9619311, can serve as key predictors of biochemical recurrence and disease prognosis of prostate cancer.

Keywords: prostate cancer; TIMP3; polymorphism; biochemical recurrence (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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