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
Hepatocellular carcinoma (HCC) often develops from chronic hepatitis B (CHB) through replication of hepatitis B virus (HBV) infection. Calcium (Ca<sup>2+</sup>) signaling plays an essential role in HBV replication. Store-operated calcium (SOC) channels are a major pathway of Ca<sup>...
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doaj-ac3b7728684f42d9bde0a02fd1530de62020-11-25T04:05:27ZengMDPI AGBiology2079-77372020-11-01938838810.3390/biology9110388Evaluation for the Genetic Association between Store-Operated Calcium Influx Pathway (STIM1 and ORAI1) and Human Hepatocellular Carcinoma in Patients with Chronic Hepatitis B InfectionLalu Muhammad Irham0Wan-Hsuan Chou1Yu-Shiuan Wang2Wirawan Adikusuma3Henry Sung-Ching Wong4Dyah Aryani Perwitasari5Wan-Chen Huang6Ben-Kuen Chen7Hwai-I Yang8Wei-Chiao Chang9Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanDepartment of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanInstitute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, TaiwanDepartment of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanDepartment of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanFaculty of Pharmacy, University of Ahmad Dahlan, Yogyakarta 55164, IndonesiaInstitute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, TaiwanPh.D. Program for translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanDepartment of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanHepatocellular carcinoma (HCC) often develops from chronic hepatitis B (CHB) through replication of hepatitis B virus (HBV) infection. Calcium (Ca<sup>2+</sup>) signaling plays an essential role in HBV replication. Store-operated calcium (SOC) channels are a major pathway of Ca<sup>2+</sup> entry into non-excitable cells such as immune cells and cancer cells. The basic components of SOC signaling include the <i>STIM1</i> and <i>ORAI1</i> genes. However, the roles of <i>STIM1</i> and <i>ORAI1</i> 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 <i>STIM1</i> and <i>ORAI1</i> genes were detected using an Axiom CHB1 genome-wide array. Clinical associations of 40 polymorphisms were analyzed. Three of the <i>STIM1</i> single-nucleotide polymorphisms (SNPs) (rs6578418, rs7116520, and rs11030472) and one SNP of <i>ORAI1</i> (rs6486795) showed a trend of being associated with HCC disease (<i>p</i> < 0.05). However, after correction for multiple testing, none of the SNPs reached a significant level (<i>q</i> > 0.05); in contrast, neither <i>STIM1</i> nor <i>ORAI1</i> 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 <i>STIM1/ORAI1</i> polymorphisms and the risk of HCC progression in CHB patients.https://www.mdpi.com/2079-7737/9/11/388chronic hepatitis B (CHB)hepatocellular carcinoma (HCC)hepatitis B virus (HBV)<i>STIM1</i><i>ORAI1</i>single-nucleotide polymorphism (SNP) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 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 chronic hepatitis B (CHB) hepatocellular carcinoma (HCC) hepatitis B virus (HBV) <i>STIM1</i> <i>ORAI1</i> single-nucleotide polymorphism (SNP) |
author_facet |
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 |
author_sort |
Lalu Muhammad Irham |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
MDPI AG |
series |
Biology |
issn |
2079-7737 |
publishDate |
2020-11-01 |
description |
Hepatocellular carcinoma (HCC) often develops from chronic hepatitis B (CHB) through replication of hepatitis B virus (HBV) infection. Calcium (Ca<sup>2+</sup>) signaling plays an essential role in HBV replication. Store-operated calcium (SOC) channels are a major pathway of Ca<sup>2+</sup> entry into non-excitable cells such as immune cells and cancer cells. The basic components of SOC signaling include the <i>STIM1</i> and <i>ORAI1</i> genes. However, the roles of <i>STIM1</i> and <i>ORAI1</i> 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 <i>STIM1</i> and <i>ORAI1</i> genes were detected using an Axiom CHB1 genome-wide array. Clinical associations of 40 polymorphisms were analyzed. Three of the <i>STIM1</i> single-nucleotide polymorphisms (SNPs) (rs6578418, rs7116520, and rs11030472) and one SNP of <i>ORAI1</i> (rs6486795) showed a trend of being associated with HCC disease (<i>p</i> < 0.05). However, after correction for multiple testing, none of the SNPs reached a significant level (<i>q</i> > 0.05); in contrast, neither <i>STIM1</i> nor <i>ORAI1</i> 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 <i>STIM1/ORAI1</i> polymorphisms and the risk of HCC progression in CHB patients. |
topic |
chronic hepatitis B (CHB) hepatocellular carcinoma (HCC) hepatitis B virus (HBV) <i>STIM1</i> <i>ORAI1</i> single-nucleotide polymorphism (SNP) |
url |
https://www.mdpi.com/2079-7737/9/11/388 |
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