Evaluation for the genetic association between store-operated calcium influx pathway (Stim1 and orai1) and human hepatocellular carcinoma in patients with chronic hepatitis b infection

Lalu Muhammad Irham, Wan Hsuan Chou, Yu Shiuan Wang, Wirawan Adikusuma, Henry Sung Ching Wong, Dyah Aryani Perwitasari, Wan Chen Huang, Ben Kuen Chen, Hwai I. Yang, Wei Chiao Chang

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatocellular carcinoma (HCC) often develops from chronic hepatitis B (CHB) through replication of hepatitis B virus (HBV) infection. Calcium (Ca2+) signaling plays an essential role in HBV replication. Store-operated calcium (SOC) channels are a major pathway of Ca2+ entry into non-excitable cells such as immune cells and cancer cells. The basic components of SOC signaling include the STIM1 and ORAI1 genes. However, the roles of STIM1 and ORAI1 in HBV-mediated HCC are still unclear. Thus, long-term follow-up of HBV cohort was carried out in this study. This study recruited 3631 patients with chronic hepatitis (345 patients with HCC, 3286 patients without HCC) in a Taiwanese population. Genetic variants of the STIM1 and ORAI1 genes were detected using an Axiom CHB1 genome-wide array. Clinical associations of 40 polymorphisms were analyzed. Three of the STIM1 single-nucleotide polymorphisms (SNPs) (rs6578418, rs7116520, and rs11030472) and one SNP of ORAI1 (rs6486795) showed a trend of being associated with HCC disease (p < 0.05). However, after correction for multiple testing, none of the SNPs reached a significant level (q > 0.05); in contrast, neither STIM1 nor ORAI1 showed a significant association with HCC progression in CHB patients. Functional studies by both total internal reflection fluorescence images and transwell migration assay indicated the critical roles of SOC-mediated signaling in HCC migration. In conclusion, we reported a weak correlation between STIM1/ORAI1 polymorphisms and the risk of HCC progression in CHB patients.

Original languageEnglish
Article number388
Pages (from-to)1-14
Number of pages14
JournalBiology
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Chronic hepatitis B (CHB)
  • Hepatitis B virus (HBV)
  • Hepatocellular carcinoma (HCC)
  • ORAI1
  • Single-nucleotide polymorphism (SNP)
  • STIM1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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