Relationship Between Quantitative Trait Loci Of PAX8 And HBV Mutation And Prognosis Of Liver Cancer

Paired-box family member PAX8 encodes a transcription factor that has a role in cell differ-entiation and cell growth and may participate in the prognosis of hepatocellular carcinoma(HCC).By bioinformatics analysis,we identified several single nucleotide polymorphisms(SNPs)within a newly identified long non-coding RNA(1ncRNA)AC016683.6 as expression quantitative trait loci(eQTLs)for PAX8.Hence,we hypothesized that PAX8 eQTLs in IncRNA AC016683.6 may influence the HCC prognosis.We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment.Cox proportional hazard models were used for survival analysis with adjustments for the age,gender,smoking status,drinking status,Barcelona-Clinic Liver Cancer(BCLC)stage,and chemotherapy or TACE(transcatheter hepatic arterial chemoembolization)status.We found that the G allele of rs1110839 and the T allele of rs4848320 in PAX8was significantly associated with a better prognosis compared with the T allele of rsl 110839 and the C allele of rs4848320(adjusted HR = 0.74,95%CI= 0.61-0.91,P = 0.004 for rs1110839 and adjusted HR = 0.71,95%CI=0.54-0.94,P = 0.015 for rs4848320 in the additive model).Furthermore,the combined effect of the variant genotypes for these two SNPs was more prominent in patients with the BCLC-C stage orpatients with chemotherapy or TACE.Although the exact biological func-tion remains to be explored,our findings suggest a possible association of PAX8 eQTLs in IncRNA AC016683.6 with the HCC prognosis in Chinese population.Further large and functional studies are needed to confirm our findings.Objective:To further explore the association between HBV genotype/mutation and prognosis of HCC.Materials and methods:A prospective clinical follow-up study was conducted to detect HBV mutations/genotyping in 331 HCC patients diagnosed by histopathology or cytology from the First Affiliated Hospital of Nanjing Medical University and Nanjing Cancer Hospital,to analyze the clinical characteristics and long-term prognosis of HCC patients,and to analyze the association between HBV mutation/genotype and HCC prognosis.Results:nt1753(T vs C:adjusted HR = 0.73,95%CI= 0.55-0.97,P = 0.035)polymorphism was associated with a reduced risk of mortality in HCC patients;adjusted age,gender,smoking,alcohol consumption,BCLC staging and radiotherapy and chemotherapy,HR = 0.73,95%CI = 0.55-0.97,P = 0.035.Conclusions:Whether radiotherapy and chemotherapy,age,nt1753 and alcohol consumption are independent prognostic factors of HCC prognosis.