Chen Cheng, Ba Yanna, Li Deyang, Du Xiaohong, Lia Xin, Yang Hai, An Jiaze, Xing Jinliang, Yang Hushan, Dong Guanglong, Guo Xu
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, The Fourth Military Medical University, 169, Changle West Road, 710032 Xi'an, China.
Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, 710032 Xi'an, China.
Clin Res Hepatol Gastroenterol. 2017 Sep;41(4):378-385. doi: 10.1016/j.clinre.2016.12.002. Epub 2017 Feb 16.
Previous studies have indicated that mitochondrial genetic variations were associated with the risk of many cancers. However, there are few reports on the association between single nucleotide polymorphisms (SNPs) or haplogroups of mitochondrial DNA (mtDNA) and the risk or prognosis of hepatocellular carcinoma (HCC).
In order to investigate the predictive and prognostic role of mtDNA SNPs and haplogroups in HCC, the mitochondrial genome of 188 HCC patients and 344 healthy controls were sequenced by next generation sequencing technology. Then, logistic regression analysis was used to determine the effect of mtDNA SNP or haplogroup on risk and prognosis of HCC patients.
The haplogroup M7 had an odds ratio (OR) of 0.47 (95% CI=0.24-0.91; P=0.026) to develop HCC. The frequency of 152T/C, 199T/C, 4048G/A, 9824T/C, 15784T/C, 16185C/T and 16399A/G was significantly different between HCC patients and the controls. In addition, multivariate analysis with COX hazards model showed that the patients with haplogroup M8 had lower survival rate than the patients with haplogroup D4 (HR=2.62, 95% CI=1.03-6.68; P=0.044). Three SNPs 15784T/C, 16185C/T and 16399A/G were also identified to have a statistically significant association with postoperative survival in HCC.
To date, these results provide the first evidence that mtDNA SNPs and haplogroups may be potential risk factors for susceptibility and survival of HCC patients.
既往研究表明，线粒体基因变异与多种癌症风险相关。然而，关于线粒体DNA（mtDNA）单核苷酸多态性（SNP）或单倍群与肝细胞癌（HCC）风险或预后之间的关联报道较少。
为了研究mtDNA SNP和单倍群在HCC中的预测和预后作用，采用下一代测序技术对188例HCC患者和344例健康对照者的线粒体基因组进行测序。然后，采用逻辑回归分析确定mtDNA SNP或单倍群对HCC患者风险和预后的影响。
单倍群M7发生HCC的比值比（OR）为0.47（95%CI=0.24-0.91；P=0.026）。HCC患者与对照组之间152T/C、199T/C、4048G/A、9824T/C、15784T/C、16185C/T和16399A/G的频率存在显著差异。此外，COX风险模型多因素分析显示，单倍群M8的患者生存率低于单倍群D4的患者（HR=2.62，95%CI=1.03-6.68；P=0.044）。还发现3个SNP 15784T/C、16185C/T和16399A/G与HCC术后生存具有统计学显著关联。
迄今为止，这些结果首次证明mtDNA SNP和单倍群可能是HCC患者易感性和生存的潜在危险因素。
