Impact of tissue inhibitor of metalloproteinases-3 genetic variants on clinicopathological characteristics of urothelial cell carcinoma

Wei-Chun Weng; Ming-Hong Hsieh; Hui-Ling Chiou; Chia-Yi Lee; Chih-Hsin Tang; Lun-Ching Chang; Shian-Shiang Wang; Shun-Fa Yang

doi:10.7150/jca.81083

Impact of tissue inhibitor of metalloproteinases-3 genetic variants on clinicopathological characteristics of urothelial cell carcinoma

J Cancer. 2023 Jan 22;14(3):360-366. doi: 10.7150/jca.81083. eCollection 2023.

Authors

Wei-Chun Weng^{1

2}, Ming-Hong Hsieh^{3

4}, Hui-Ling Chiou⁵, Chia-Yi Lee⁶, Chih-Hsin Tang^{7

8

9}, Lun-Ching Chang¹⁰, Shian-Shiang Wang^{3

11

12}, Shun-Fa Yang^{13

14}

Affiliations

¹ Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
² Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
³ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁴ Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁵ School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
⁶ Department of Ophthalmology, Nobel Eye Institute, Taipei, Taiwan.
⁷ School of Medicine, China Medical University, Taichung, Taiwan.
⁸ Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
⁹ Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
¹⁰ Department of Mathematical Sciences, Florida Atlantic University, Boca Raton, FL, USA.
¹¹ Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
¹² Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan.
¹³ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
¹⁴ Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.

Abstract

To investigate the distribution of single nucleotide polymorphism (SNP) of tissue inhibitor of metalloproteinases-3 (TIMP-3) in patients with/without urothelial cell carcinoma (UCC), three loci of TIMP-3 SNPs (rs9862 C/T, rs9619311 T/C, rs11547635 C/T) were genotyped via TaqMan allelic discrimination for 424 UCC patients and 848 non-UCC participants. Furthermore, the TIMP-3 mRNA expression and its correlation with clinical characters of urothelial bladder carcinoma was analyzed using The Cancer Genome Atlas database (TCGA). The distribution of all 3 studied SNPs of TIMP-3 was insignificantly different between the UCC and non-UCC groups. However, significantly lower tumor T status was found in TIMP-3 SNP rs9862 CT + TT variant than the wild type (OR: 0.515, 95% CI: 0.289-0.917, P = 0.023). Moreover, the muscle invasive tumor type was significantly correlated to the TIMP-3 SNP rs9619311 TC + CC variant in the non-smoker subgroup (OR: 2.149, 95% CI: 1.143-4.039, P = 0.016). With the TIMP-3 expression data provided in TCGA, significantly higher TIMP-3 mRNA expression was observed in UCC with high tumor stage (P < 0.0001), high tumor T status (P < 0.0001) and high lymph node status (P = 0.0005). In conclusions, TIMP-3 SNP rs9862 variant is associated with lower tumor T status of UCC while TIMP-3 SNP rs9619311 variant is correlated to muscle invasive UCC development in non-smoker.

Keywords: single nucleotide polymorphism, urothelial cell carcinoma; tissue inhibitor of metalloproteinases-3, tobacco, tumor stage.