Yulong Chen1, Xunjun Yang1,2, Yao Chen3, Guorong Chen3, Cheryl A Winkler4, Ping An5, Jianxin Lyu6,7. 1. Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China. 2. Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. 3. Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. 4. Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. 5. Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. ping.an@nih.gov. 6. Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China. jxlu313@163.com. 7. Zhejiang Provincial People's Hospital, Affiliated Hospital of Hangzhou Medical College, Zhejiang, Hangzhou, China. jxlu313@163.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: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. METHODS: We genotyped three exonic SOAT1 variants (rs10753191, V323V; rs3753526, L475L; rs13306731, Q526R) tagging most variations in the gene, in 221 HCCpatients 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. RESULTS: 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). CONCLUSION: 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.
Entities:
Keywords:
Hepatocellular carcinoma; SOAT1; Single nucleotide polymorphism; Susceptibility
Authors: C C Chang; N Sakashita; K Ornvold; O Lee; E T Chang; R Dong; S Lin; C Y Lee; S C Strom; R Kashyap; J J Fung; R V Farese; J F Patoiseau; A Delhon; T Y Chang Journal: J Biol Chem Date: 2000-09-08 Impact factor: 5.157
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702