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Mitochondrial DNA Haplogroup N9a Negatively Correlates with Incidence of Hepatocellular Carcinoma in Northern China.

Abstract：

: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.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Hua S,Li M,Zhao Q,Wang J,Zhou Y,Liu J,Fang H,Jiang M,Shen L

doi

10.1016/j.omtn.2019.09.001

subject

Has Abstract

pub_date

2019-12-06 00:00:00

pages

332-340

issn

2162-2531

pii

S2162-2531(19)30246-X

journal_volume

18

pub_type

杂志文章

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