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Genetic variants of dipeptidyl peptidase IV are linked to the clinicopathologic development of prostate cancer |
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| Authors: | Yu-Ching Wen Chia-Yen Lin Chi-Hao Hsiao Shian-Shiang Wang Hsiang-Ching Huang Yung-Wei Lin Kuo-Hao Ho Lun-Ching Chang Shun-Fa Yang Ming-Hsien Chien |
| Institution: | 1. Department of Urology, School of Medicine, College of Medicine and TMU Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei, Taiwan
Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Contribution: Conceptualization (equal), Data curation (equal), Funding acquisition (equal), Writing - original draft (equal);2. Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan School of Medicine, Chung Shan Medical University, Taichung, Taiwan School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Contribution: Data curation (equal), Resources (equal);3. Department of Urology, School of Medicine, College of Medicine and TMU Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei, Taiwan Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Contribution: Methodology (equal);4. Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan School of Medicine, Chung Shan Medical University, Taichung, Taiwan Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan Contribution: Data curation (equal), Resources (equal);5. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan Contribution: Methodology (equal), Software (equal);6. Department of Urology, School of Medicine, College of Medicine and TMU Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei, Taiwan Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan International Master/PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Contribution: Conceptualization (equal);7. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan Contribution: Data curation (equal), Software (equal);8. Department of Mathematical Sciences, Florida Atlantic University, Boca Raton, Florida, USA Contribution: Software (equal);9. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan;10. International Master/PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan |
| Abstract: | CD26/dipeptidyl peptidase IV (DPP4) is a multifunctional cell-surface glycoprotein widely found in many cell types, and a soluble form is present in body fluids. There is longstanding evidence indicating a tumour-promoting or -suppressive role of DPP4 in different cancer types. However, studies focusing on the impacts of genetic variants of DPP4 on cancers are very rare. Herein, we conducted a case–control study to evaluate whether single-nucleotide polymorphisms (SNPs) of DPP4 were associated with the risk or clinicopathologic development of prostate cancer (PCa). We genotyped four loci of DPP4 SNPs, including rs7608798 (A/G), rs3788979 (C/T), rs2268889 (T/C) and rs6741949 (G/C), using a TaqMan allelic discrimination assay in 704 PCa patients and 704 healthy controls. Our results showed that PCa patients with the DPP4 rs7608798 AG+GG genotype or rs2268889 TC+CC genotype had a higher risk of developing an advanced clinical primary tumour (cT) stage (adjusted odds ratio (AOR): 1.680, 95% confidence interval (CI): 1.062–2.659, p = 0.025; AOR: 1.693, 95% CI: 1.092–2.624, p = 0.018). Additionally, in The Cancer Genome Atlas (TCGA) database, we observed that lower DPP4 expression levels were correlated with higher Gleason scores, advanced cT and pathological stages, tumour metastasis, and shorter progression-free survival rates in PCa patients. Furthermore, overexpression of DPP4 suppressed migration/invasion of metastatic PC3 PCa cells. Our findings suggest that DPP4 levels may affect the progression of PCa, and the DPP4 rs7608798 and rs2268889 SNPs are associated with the clinicopathologic development of PCa in a Taiwanese population. |
| Keywords: | clinicopathologic development dipeptidyl peptidase IV prostate cancer single-nucleotide polymorphism |