Open AccessA common regulatory variant in SLC 35B4 influences the recurrence and survival of prostate cancer
Author(s) -
Huang Eric Y.,
Chang YuJia,
Huang ShuPin,
Lin Victor C.,
Yu ChiaCheng,
Huang ChaoYuan,
Yin HsinLing,
Chang TaYuan,
Lu TeLing,
Bao BoYing
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13649
Subject(s) - prostate cancer , snp , single nucleotide polymorphism , prostatectomy , oncology , cancer , prostate , biology , medicine , biochemical recurrence , in silico , gene , bioinformatics , genetics , genotype
Single nucleotide polymorphisms ( SNP s) within the regulatory elements of a gene can alter gene expression, making these SNP s of prime importance for candidate gene association studies. We aimed to determine whether such regulatory variants are associated with clinical outcomes in three cohorts of patients with prostate cancer. We used Regulome DB to identify potential regulatory variants based on in silico predictions and reviewed genome‐wide experimental findings. Overall, 131 putative regulatory SNP s with the highest confidence score on predicted functionality were investigated in two independent localized prostate cancer cohorts totalling 458 patients who underwent radical prostatectomy. The statistically significant SNP s identified in these two cohorts were then tested in an additional cohort of 504 patients with advanced prostate cancer. We identified one regulatory SNP s, rs1646724, that are consistently associated with increased risk of recurrence in localized disease ( P = .003) and mortality in patients with advanced prostate cancer ( P = .032) after adjusting for known clinicopathological factors. Further investigation revealed that rs1646724 may affect expression of SLC 35B4 , which encodes a glycosyltransferase, and that down‐regulation of SLC 35B4 by transfecting short hairpin RNA in DU 145 human prostate cancer cell suppressed proliferation, migration and invasion. Furthermore, we found increased SLC 35B4 expression correlated with more aggressive forms of prostate cancer and poor patient prognosis. Our study provides robust evidence that regulatory genetic variants can affect clinical outcomes.