Xiaoyu Long1, Xiaoyan Wang2, Yibing Chen1, Xu Guo1, Feng Zhou3, Yongguo Fan4, Naijian Ge5, Mei Guo6, Zhaohui Zhang7, Guanglong Dong8. 1. Fourth Military Medical University, Experimental Teaching Center of Basic Medicine, State Key Laboratory of Cancer Biology, Xi'an, China. 2. Fourth Military Medical University, Experimental Teaching Center of Basic Medicine, State Key Laboratory of Cancer Biology, Xi'an, China; Shaanxi Cancer Hospital, Department of Breast Cancer Center, Xi'an, China. 3. Fourth Military Medical University, Tangdu Hospital, Department of General Surgery, Xi'an, China; Xuzhou Medical University, Huaihai Hospital, Department of General Surgery, Xuzhou, Jiangsu, China. 4. Fourth Military Medical University, Tangdu Hospital, Department of General Surgery, Xi'an, China. 5. Second Military Medical University, Eastern Hepatobiliary Surgery Hospital, Department of Radioactive Intervention, Shanghai, China. 6. PLA 451 Hospital, Xi'an, China. 7. Xuzhou Medical University, Huaihai Hospital, Department of General Surgery, Xuzhou, Jiangsu, China. Electronic address: zzhlyn@163.com. 8. The General Hospital of PLA, Department of General Surgery, Beijing, China. Electronic address: guanglongdong@126.com.
Abstract
BACKGROUND: POLG is a gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, which is involved in the replication of mitochondrial DNA. Genetic variants in mitochondrial DNA polymerase-γ (POLG) have been associated with several malignancies. However, as an important metabolic tissue, association between genetic polymorphisms of POLG and the prognosis and mitochondrial DNA (mtDNA) content in hepatocellular carcinoma (HCC) remains unknown. Here we investigated the association between in POLG with the prognosis and mitochondrial DNA (mtDNA) content in hepatocellular carcinoma (HCC). METHODS: Three nucleotide polymorphisms (SNPs) of rs1061316, rs2247233 and rs758130 in POLG were examined in 416 patients from two cohorts undergoing transcatheter arterial chemoembolization treatment. Leukocyte mtDNA content from 216 patients in cohort 2 was measured using a real-time PCR-based method. The association of SNPs with prognosis and of mtDNA content of patients was analyzed. RESULTS: The rs758130 in POLG gene was significantly associated with the prognosis of patients in a dose-dependent manner. Moreover, GG genotype in rs1061316 showed significantly high mtDNA content, an indicator of better prognosis. CONCLUSIONS: Our study for the first time demonstrates that rs1061316 and rs758130 in POLG is associated with the prognosis and leukocyte mtDNA content in HCC patients.
BACKGROUND:POLG is a gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, which is involved in the replication of mitochondrial DNA. Genetic variants in mitochondrial DNA polymerase-γ (POLG) have been associated with several malignancies. However, as an important metabolic tissue, association between genetic polymorphisms of POLG and the prognosis and mitochondrial DNA (mtDNA) content in hepatocellular carcinoma (HCC) remains unknown. Here we investigated the association between in POLG with the prognosis and mitochondrial DNA (mtDNA) content in hepatocellular carcinoma (HCC). METHODS: Three nucleotide polymorphisms (SNPs) of rs1061316, rs2247233 and rs758130 in POLG were examined in 416 patients from two cohorts undergoing transcatheter arterial chemoembolization treatment. Leukocyte mtDNA content from 216 patients in cohort 2 was measured using a real-time PCR-based method. The association of SNPs with prognosis and of mtDNA content of patients was analyzed. RESULTS: The rs758130 in POLG gene was significantly associated with the prognosis of patients in a dose-dependent manner. Moreover, GG genotype in rs1061316 showed significantly high mtDNA content, an indicator of better prognosis. CONCLUSIONS: Our study for the first time demonstrates that rs1061316 and rs758130 in POLG is associated with the prognosis and leukocyte mtDNA content in HCC patients.
Authors: Siti Muslihah Abd Radzak; Siti Zulaikha Nashwa Mohd Khair; Farizan Ahmad; Azim Patar; Zamzuri Idris; Abdul Aziz Mohamed Yusoff Journal: Int J Mol Med Date: 2022-06-17 Impact factor: 5.314