Impacts of the SOAT1 genetic variants and protein expression on HBV-related hepatocellular carcinoma.

Impacts of the SOAT1 genetic variants and protein expression on HBV-related hepatocellular carcinoma.
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SOAT 1基因变异和蛋白表达对HBV相关肝细胞癌的影响

DOI:
10.1186/s12885-021-08245-1
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发表时间:
2021-05-26
期刊:
影响因子:
3.8
通讯作者:
Lyu J
Lyu J
中科院分区:
医学2区
文献类型:
--
作者:
Chen Y;Yang X;Chen Y;Chen G;Winkler CA;An P;Lyu J

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B型肝炎病毒(HBV)相关的肝细胞癌(HCC)仍然是一个主要的公共卫生问题,其发病机制尚未解决。最近的一项蛋白质组学研究发现脂质酶固醇O-酰基转移酶(SOAT 1)参与HCC的进展。我们的目的是探讨SOAT 1基因变异与HCC之间的关系。我们对221名HCC患者和229名健康个体的SOAT 1基因的三个外显子变异(rs 10753191,V323 V; rs3753526,L475 L; rs 13306731,Q526 R)进行了基因分型,以评估SOAT 1基因变异对HCC发生风险的影响。我们进一步进行了免疫组化比较SOAT 1蛋白在42对肿瘤和相邻非肿瘤组织中的表达水平。我们发现rs 10753191(比值比(OR)= 0.58,P = 0.04)和单倍型TGA(OR = 0.40,P = 0.01)与调整血脂水平后HCC风险降低相关。免疫组化结果显示,SOAT 1在肿瘤组织中的表达明显高于癌旁组织(P < 0.001)。这项研究首次揭示了SOAT 1基因变异与宿主对HCC发生的易感性相关。我们的研究结果表明SOAT 1在HCC发展中的作用,值得进一步阐明。在线版本包含补充材料,可通过10.1186/s12885-021-08245-1获得。
Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a major public health problem and its pathogenesis remains unresolved. A recent proteomics study discovered a lipid enzyme Sterol O-acyltransferase (SOAT1) involvement in the progression of HCC. We aimed to explore the association between SOAT1 genetic variation and HCC. We genotyped three exonic SOAT1 variants (rs10753191, V323V; rs3753526, L475L; rs13306731, Q526R) tagging most variations in the gene, in 221 HCC patients and 229 healthy individuals, to assess the impact of SOAT1 gene variation on risk of HCC occurrence. We further conducted immunohistochemistry to compare SOAT1 protein expression levels in 42 paired tumor and adjacent non-tumor tissues. We found that rs10753191 (Odds ratio (OR) = 0.58, P = 0.04) and a haplotype TGA (OR = 0.40, P = 0.01) were associated with reduced HCC risk after adjusting for lipid levels. In the immunohistochemistry experiment, we found that the protein expression of SOAT1 was significantly increased in the tumor compared with adjacent tissue (P < 0.001). This study revealed for the first time SOAT1 genetic variation that associates with host susceptibility to HCC occurrence. Our results suggest a role of SOAT1 in the HCC development, which warrants further elucidation. The online version contains supplementary material available at 10.1186/s12885-021-08245-1.
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