ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2023; 14(3):360-366. doi:10.7150/jca.81083 This issue Cite
Research Paper
Impact of tissue inhibitor of metalloproteinases-3 genetic variants on clinicopathological characteristics of urothelial cell carcinoma
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
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