Impacts of WNT1-inducible signaling pathway protein 1 polymorphism on hepatocellular carcinoma development

PLoS One. 2018 Jun 11;13(6):e0198967. doi: 10.1371/journal.pone.0198967. eCollection 2018.

Abstract

Background: WNT1-inducible signaling pathway protein 1 (WISP1) is a member of CCN protein family and a downstream target of β-catenin. Aberrant WISP1 expression is associated with carcinogenesis. In the current study, we focused on examining WISP1 single nucleotide polymorphisms (SNPs) to elucidate hepatocellular carcinoma (HCC) clinicopathologic characteristics.

Methodology/principal findings: The WISP1 SNPs rs2977530, rs2977537, rs2929973, rs2929970, rs62514004, and rs16893344 were analyzed by real-time polymerase chain reaction in 332 patients with HCC and 664 cancer-free controls.

Results: The patients with higher frequencies of WISP1 rs62514004 (AG + GG) and rs16893344 (CT + TT) variants revealed a lower risk to reach a later clinical stage compared with their wild-type carriers. Furthermore, individuals who carried WISP1 rs62514004 and rs16893344 haplotype G-T showed a greater synergistic effect combined with alcohol drinking on HCC development (AOR = 26.590, 95% CI = 9.780-72.295).

Conclusions: Our results demonstrated that the HCC patients with WISP1 SNPs are associated with HCC development, and WISP1 SNPs may serve as markers or therapeutic targets for HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alcohol Drinking
  • Alleles
  • CCN Intercellular Signaling Proteins / genetics*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins / genetics*
  • Statistics, Nonparametric

Substances

  • CCN Intercellular Signaling Proteins
  • CCN4 protein, human
  • Proto-Oncogene Proteins

Grants and funding

This study was supported by a grant (CSH-2017-C-019) from Chung Shan Medical University Hospital and a research Grant from Chung Shan Medical University, Taiwan (G103N0005). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.