A common regulatory variant in SLC35B4 influences the recurrence and survival of prostate cancer

Eric Y. Huang, Yu Jia Chang, Shu Pin Huang, Victor C. Lin, Chia Cheng Yu, Chao Yuan Huang, Hsin Ling Yin, Ta Yuan Chang, Te Ling Lu, Bo Ying Bao

Research output: Contribution to journalArticle

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Abstract

Single nucleotide polymorphisms (SNPs) within the regulatory elements of a gene can alter gene expression, making these SNPs 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 RegulomeDB to identify potential regulatory variants based on in silico predictions and reviewed genome-wide experimental findings. Overall, 131 putative regulatory SNPs 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 SNPs identified in these two cohorts were then tested in an additional cohort of 504 patients with advanced prostate cancer. We identified one regulatory SNPs, 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 SLC35B4, which encodes a glycosyltransferase, and that down-regulation of SLC35B4 by transfecting short hairpin RNA in DU145 human prostate cancer cell suppressed proliferation, migration and invasion. Furthermore, we found increased SLC35B4 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.

LanguageEnglish
Pages3661-3670
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume22
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

Fingerprint

Prostatic Neoplasms
Single Nucleotide Polymorphism
Recurrence
Survival
Glycosyltransferases
Genetic Association Studies
Prostatectomy
Computer Simulation
Small Interfering RNA
Down-Regulation
Cell Proliferation
Genome
Gene Expression
Mortality
Genes

Keywords

  • multi-stage association study
  • prognosis
  • prostate cancer
  • regulatory variant
  • SLC35B4

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

A common regulatory variant in SLC35B4 influences the recurrence and survival of prostate cancer. / Huang, Eric Y.; Chang, Yu Jia; Huang, Shu Pin; Lin, Victor C.; Yu, Chia Cheng; Huang, Chao Yuan; Yin, Hsin Ling; Chang, Ta Yuan; Lu, Te Ling; Bao, Bo Ying.

In: Journal of Cellular and Molecular Medicine, Vol. 22, No. 7, 01.07.2018, p. 3661-3670.

Research output: Contribution to journalArticle

Huang, EY, Chang, YJ, Huang, SP, Lin, VC, Yu, CC, Huang, CY, Yin, HL, Chang, TY, Lu, TL & Bao, BY 2018, 'A common regulatory variant in SLC35B4 influences the recurrence and survival of prostate cancer' Journal of Cellular and Molecular Medicine, vol. 22, no. 7, pp. 3661-3670. https://doi.org/10.1111/jcmm.13649
Huang, Eric Y. ; Chang, Yu Jia ; Huang, Shu Pin ; Lin, Victor C. ; Yu, Chia Cheng ; Huang, Chao Yuan ; Yin, Hsin Ling ; Chang, Ta Yuan ; Lu, Te Ling ; Bao, Bo Ying. / A common regulatory variant in SLC35B4 influences the recurrence and survival of prostate cancer. In: Journal of Cellular and Molecular Medicine. 2018 ; Vol. 22, No. 7. pp. 3661-3670.
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