The Association Study For The Relationship Between Regulome-SNP And Survival Rate Of Primary Liver Cancer

Background:Primary liver cancer is a malignant tumor of hepatocytes or intrahepatic bile duct epithelial cells.Liver cancer has a high incidence rate in China.It is one of the common malignant tumors in China and a disease that seriously endangers human life and health.Liver cancer has a high mortality rate and a poor prognosis,the early diagnosis rate of PHC is low and it has developed into middle and late stage at the time of discovery.The factors that affect the survival rate of primary liver cancer are very complex.Prediction from RNA level and protein level alone cannot accurately reflect its survival factors.With the in-depth development of molecular biology and genetic research,it is found that oncogenes,tumor suppressor genes,microRNA3 and their target single nucleotide polymorphisms(SNPs)are closely related to the survival rate of primary liver cancer.The possible molecular basis of liver cancer is the result of the interaction of multiple genetic factors and their specific combinations,viruses,lifestyles and eating habits.Therefore,to find specific Regulome-SNP sites closely related to the survival rate of patients with intermediate and advanced PHC.Objectives:To investigate the correlation between RPS6KA2 gene locus rs9366065、HLA-A gene locus rs3132682 and liver cancer,its significance in the diagnosis of liver cancer survival rate,and to provide a reliable experimental basis for predicting PHC survival rate and prognosis.Methods:Database and prediction software were used to screen 300 SNPs with minor allele frequency(MAF)greater than 10%in potential liver cancer-related gene regions related to liver cancer;Collect blood samples from 366 patients with primary liver cancer diagnosed at Yanbian Hospital and Yanbian Cancer Hospital from June 2011 to August 2017;DNA was extracted strict conformity with the instructions of the kit(260/230 and 260/280 wavelengths>1.5 and total amount reached 1.5μg);The frequency of gene distribution in PHC patients was detected mainly by the method of gene typing based on Sequenom MassARRAYOR mass spectrometry,and the genotyping of patients was Verified by PCR-RFLP technology.The correlation between the distribution frequency of Regulome-SNP and survival rate was analyzed by statistical methods,Screening for statistically significant SNPs based on patient complete clinical information.For example:Logistic regression model is used to analyze the influencing factors of PHC.The overall survival rate was calculated using the Kaplan-Meier survival analysis.A multivariate Cox regression risk model was used to calculate cHR,95%CI,and its corresponding P value.Results:The average survival time of patients with primary liver cancer was(24.36±25.46)months;The frequencies of the rs9366065A and C alleles were not significantly different among clinical features;The analysis of the correlation between SNPs in HCC-related genes and clinical data showed that:Among the 290 SNPs of the gene related liver cancer,the overall survival rate of the RPS6KA2 locus rs9366065(P=0.024)and HLA-A locus rs3132682(P=0.024)were statistically significant;Patients with the rs93 66065AA or CA genotype had significantly better survival than the rs9366065CC genotype(HR=0.656,95%CI=0.475-0.905,P=0.01),the survival of patients with rs313268CC genotype was also protective compared with rs313268GG+GA genotype(HR=0.712,95%CI=0.558-0.910,P=0.01);Adjuvant therapy and rs313268CC genotype were protective factors that affect the survival of liver cancer patients by multivariate COX regression,and rs9366065 mutant gene locus CC was a risk factor for the survival of liver cancer.Conclusions:The rs9366065(A>C)and rs3132682CC(G>C)polymorphisms may affect the survival of patients with primary liver cancer.Analysis of rs9366065(A>C)and rs3132682(G>C)polymorphisms can help identify patients with a high risk of poor prognosis.