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

Biology

Wirawan Adikusuma¹  Henry Sung-Ching Wong¹  Lalu Muhammad Irham¹  Wei-Chiao Chang¹  Wan-Hsuan Chou¹  Dyah Aryani Perwitasari²  Hwai-I Yang³  Yu-Shiuan Wang⁴  Wan-Chen Huang⁴  Ben-Kuen Chen⁵ 

[1] Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan;Faculty of Pharmacy, University of Ahmad Dahlan, Yogyakarta 55164, Indonesia;Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan;Ph.D. Program for translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan;

关键词: chronic hepatitis B (CHB);    hepatocellular carcinoma (HCC);    hepatitis B virus (HBV);    STIM1;    ORAI1;    single-nucleotide polymorphism (SNP);   

DOI  :  10.3390/biology9110388

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown