Mitochondrial DNA Haplogroup N9a Negatively Correlates with Incidence of Hepatocellular Carcinoma in Northern China
Autor: | Meinan Li, Jiangtao Liu, Lijun Shen, Hezhi Fang, Shixuan Hua, Junyi Wang, Yaping Zhou, Minghua Jiang, Qiongya Zhao |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
gene set enrichment analysis Mitochondrial DNA haplogroup mtSNP mitochondrial DNA Biology Haplogroup Article 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Genetics GSEA mtDNA mitochondrial SNP lcsh:RM1-950 Cancer Odds ratio hepatocellular carcinoma Hepatitis B medicine.disease 030104 developmental biology lcsh:Therapeutics. Pharmacology cybrid 030220 oncology & carcinogenesis Hepatocellular carcinoma Molecular Medicine Liver cancer Human mitochondrial DNA haplogroup |
Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 18, Iss, Pp 332-340 (2019) |
ISSN: | 2162-2531 |
Popis: | Mitochondrial DNA (mtDNA) haplogroups are associated with various types of cancer; however, the molecular mechanisms by which mtDNA haplogroups affect primary hepatocellular carcinoma (HCC) are not known. In this study, we carried out a case-control study on 388 HCC patients and 511 geographically matched asymptomatic control subjects in northern China. We found that mtDNA haplogroup N9a and its diagnostic SNP, m.16257C > A, negatively correlated with the incidence of HCC in northern China (odds ratio [OR] 0.290, 95% confidence interval [CI] 0.123–0.685, p = 0.005), particularly in patients with infection of hepatitis B/C virus (HBV/HCV) (for haplogroup N9a: OR 0.213, 95% CI 0.077–0.590, p = 0.003; for m.16257C > A: OR 0.262, 95% CI 0.107–0.643, p = 0.003). However, mtDNA haplogroup N9a is not associated with clinical characteristics of HCC including serum alpha-fetoprotein (AFP) level and tumor size. In addition, cytoplasmic hybrid (cybrid) cells with N9a haplogroup (N9a10a and N9a1) had transcriptome profiles distinct from those with non-N9a (B5, D4, and D5) haplogroups. Gene set enrichment analysis (GSEA) showed that metabolic activity varied significantly between N9a and non-N9a haplogroups. Moreover, cells with haplogroup N9a negatively correlated with cell division and multiple liver cancer pathways compared with non-N9a cells. Although it is still unclear how N9a affects the aforementioned GSEA pathways, our data suggest that mtDNA haplogroup N9a is negatively correlated with the incidence and progression of HCC in northern China. Keywords: mitochondrial DNA, mtDNA, haplogroup, mitochondrial SNP, mtSNP, hepatocellular carcinoma, cybrid, gene set enrichment analysis, GSEA |
Databáze: | OpenAIRE |
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