| Primary liver cancer is one of the most common in the world at present. According to the latest epidemiological report,nearly 800,000 of new primary liver cancers occur each year, about 750,000 patients die of liver cancers. The mortality and incidence of liver cancer rank second and fourth respectively. The situation of China is even worse,and more than 55% of the new HCC cases in the world come from Chinese. Hepatocellular carcinoma(HCC) is the most common liver cancer in the world, accounting for more than 90% of the liver cancer.According to the different stages of liver cancers, patients tend to be given individual comprehensive treatments, such as surgery, chemotherapy, interventional therapy, etc. Among them, the radical hepatectomy is the preferred treatment for liver cancer. However, many patients were often to be diagnosed with advanced HCC when they first gone to hospital, and too late to be given surgeries. Therefore, early detection and accurate assessment of HCC is of great importance.At present, plasma tumor marker detection is an ideal method for screening patients at an early stage and prefiguring their prognosis. Plasma alpha fetoprotein(AFP) is the most widely used tumor marker for HCC. However, it becomes less sensitive in detecting HCC at early stage and is limited by the false positivity in patients with active hepatitis. About 80% of the HCC patients would have rised AFP levels, but also means that 20% of the patients will be missed. Thus, looking for some new tumor markers to detect the tumorigenesis and predict progression of HCC independent or as a supplement of AFP is an urgent need.Mitochondria are ubiquitous and important organelles in eukaryotic cells, which has its own genome(mt DNA),which has a large number of mutations that have segregated during evolution. Single nucleotide polymorphism(SNP) is one of the most common mitochondria mutations, which has been proven to be associated with a variety of diseases and tumours.A number of SNPs in linkage disequilibrium formed a haplogroup. In recent years, studies have showed that SNPs and haplogroups play important roles in predicting the incidence and prognosis of tumor, such as gastric cancer, breast cancer, lung cancer etc. However, the relationship between the incidence or mortality of HCC and SNPs or haplogroups is not clear now.Purpose: In order to improve the level of diagnosis and treatment for HCC, and seek for more effective molecular markers, in this study we devote ourselves to investigating the predictive and prognostic role of mt DNA SNPs and haplogroups in HCC.Methods: We collect 188 HCC patients from Xijing Hospital and Eastern Hepatobiliary Surgery Hospital as experience group, and choose 344 normal Chinese individuals from Phypotree home mitochondrial genome sequence database as control group. Whole mitochondrial genomes were sequenced by Illumina Hiseq 2000. Furthermore, the mt DNA haplogroup classification was determined according to the phylogenetic tree Build 16 of global human mt DNA using the soft Mitotool. Varieties of statistical methods were used to research the influence of SNP and haplogroup on the risk and prognosis of HCC patients.Result: Logistic regression analysis was used to determine the effect of SNP or mt DNA haplogroup on the disease onset. 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 were significantly different between HCC patients and the controls. In addition, multivariate analysis with COX hazards model showed that the patients with haplogroup M8 had poor survival when compared with the patients with haplogroup D4(HR = 2.80, 95% CI = 1.09–7.18; P = 0.033). Three SNPs 15784T/C, 16185C/T and 16399A/G were also identified to have a statistically significant association with postoperative survival in HCC.Conclusion: To date, these results are the first evidences showing that mt DNA SNPs and haplogroups may be potential risk factors for susceptibility and survival of HCC patients. The most important finding is that haplogroup M7 is associated with significantly decreased risk of HCC. We also found that 7 SNPs have significant different distribution between HCC and control. Furthermore, our data demonstrated that haplogroup M8 and 3 mt DNA SNPs were associated with survival of HCC. To the best of our knowledge, this is the first report to evaluate the effect of genetic variations in mt DNA on HCC susceptibility and survival. |
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