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Cancer Med. 2019 Jun;8(6):2777-2783. doi: 10.1002/cam4.2163. Epub 2019 Apr 16.

Effect of genetic variants in cell adhesion pathways on the biochemical recurrence in prostate cancer patients with radical prostatectomy.

Yu CC1,2,3, Chen LC4, Lin VC5,6, Huang CY7, Cheng WC8,9,10, Hsieh AR11, Chang TY12, Lu TL13, Lee CH14,15, Huang SP14,15,16,17, Bao BY13,18,19.

Author information

1
Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
2
Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
3
Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung, Taiwan.
4
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
5
Department of Urology, E-Da Hospital, Kaohsiung, Taiwan.
6
School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
7
Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
8
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
9
Research Center for Tumor Medical Science, China Medical University, Taichung, Taiwan.
10
Drug Development Center, China Medical University, Taichung, Taiwan.
11
Graduate Institute of Biostatistics, China Medical University, Taichung, Taiwan.
12
Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan.
13
Department of Pharmacy, China Medical University, Taichung, Taiwan.
14
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
15
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
16
Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
17
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
18
Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
19
Department of Nursing, Asia University, Taichung, Taiwan.

Abstract

The aberrant expression of cell adhesion molecules is a hallmark of epithelial-to-mesenchymal transition, resulting in the transformation of cancer cells to a more aggressive phenotype. This study investigated the association between genetic variants in cell adhesion pathways and the prognosis of patients with prostate cancer following radical prostatectomy (RP). A total of 18 haplotype-tagging single-nucleotide polymorphisms (SNPs) in eight cancer-related adhesion molecules were genotyped in 458 prostate cancer patients, followed by the replication of the top SNPs in an additional set of 185 patients. Log-rank test and multivariate Cox regression analysis adjusted for covariates were used to evaluate associations with the risk of biochemical recurrence (BCR) after RP. In the discovery set, four SNPs in CDH2 were marginally associated with BCR. Among these, CDH2 rs643555C > T was found to be associated with BCR in the replication set. Patients with rs643555TT genotype had a significantly shorter BCR-free survival compared with those with CC/CT genotypes in the combined analysis (adjusted hazard ratio 1.78, 95% confidence interval 1.19-2.67, P = 0.005). Additional analyses revealed that rs643555T was associated with higher expression of CDH2, and upregulated CDH2 was correlated with tumor aggressiveness and shortened BCR-free survival. In conclusion, rs643555C > T affects CDH2 expression, and thus influences BCR in localized prostate cancer patients treated with RP. CDH2 rs643555 may be a promising biomarker to identify patients at high risk of poor prostate cancer prognosis.

KEYWORDS:

CDH2; biomarker; cell adhesion; prognosis; prostate cancer

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