TY - JOUR
T1 - 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
AU - Irham, Lalu Muhammad
AU - Chou, Wan Hsuan
AU - Wang, Yu Shiuan
AU - Adikusuma, Wirawan
AU - Wong, Henry Sung Ching
AU - Perwitasari, Dyah Aryani
AU - Huang, Wan Chen
AU - Chen, Ben Kuen
AU - Yang, Hwai I.
AU - Chang, Wei Chiao
N1 - Funding Information:
Funding: This project was supported by grants from the Ministry of Science and Technology, Taiwan (MOST105-2628-B-038 -001 -MY4 and MOST108-2314-B-038-027).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Chronic hepatitis B (CHB)
KW - Hepatitis B virus (HBV)
KW - Hepatocellular carcinoma (HCC)
KW - ORAI1
KW - Single-nucleotide polymorphism (SNP)
KW - STIM1
UR - http://www.scopus.com/inward/record.url?scp=85095839423&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095839423&partnerID=8YFLogxK
U2 - 10.3390/biology9110388
DO - 10.3390/biology9110388
M3 - Article
AN - SCOPUS:85095839423
SN - 2079-7737
VL - 9
SP - 1
EP - 14
JO - Biology
JF - Biology
IS - 11
M1 - 388
ER -
