TERT Promoter Mutation In Hepatocellular Carcinoma And Renal Pelvic Carcinoma

BackgroundHepatocellular carcinoma(HCC)and renal pelvic carcinoma(RPC)are common malignant tumors in the world.Their common characteristics are high proliferation,insidious onset,high malignancy,difficult early diagnosis and drug resistance.The occurrence,development and prognosis of tumors are the results of multi-genes,multi-pathways and multi-stages.Exploring the mechanism of tumorigenesis and development is of great significance for the diagnosis and treatment of the diseases.The regulation of telomerase activity plays an important role in human aging and diseases such as tumors.Telomerase reverse transcriptase(TERT)is the key regulator of telomerase activity.TERT expression plays an important role in cell immortalization and tumor progression,and the increase of TERT replication will lead to the occurrence of tumors.Recently,research has found that TERT promoter mutations play an important role in the process of the activation of telomerase.This study was to investigate the mutation of TERT promoter in HCC and RPC,and to analyze its role in the occurrence and development of HCC and RPC,and to provide a new theoretical basis for clinical diagnosis and prognosis.ObjectiveTo explore the mutations of TERT promoter in HCC and RPC patients,and to analyze the correlation between TERT promoter mutations and clinicopathological features and prognosis of HCC and RPC patients,and to provide a new theoretical basis for clinical diagnosis and prognosis.MethodsIn this study,113 cases of HCC tissue specimens and 97 cases of RPC tissue specimens and corresponding normal tissues adjacent to the cancer were collected in the First Affiliated Hospital of Zhengzhou University from September 2006 to October 2011.PCR and Sanger sequencing techniques were used to detect the mutation of TERT promoter in these tissues.The association between TERT promoter mutations and clinicopathological parameters of HCC and RPC was to assess.Kaplan-Meier method was used for survival analysis,and Log-rank test was used to compare the survival time between groups.Cox proportional hazards regression model was used to analyze the influence of different factors on the prognosis of patients.The test level was taken from bilateral ?=0.05.Results1.Sequencing analyses revealed TERT promoter mutation rate was 33.6%(38/113)in HCC,including 30 cases of C228 T mutation,8 cases of C250 T mutation.TERT promoter mutation rate was 62.9%(61/97)in RPC,including 52 cases of C228 T mutation,9 cases of C250 T mutation.None of TERT promoter mutation was detected in adjacent normal tissues.2.Among HCC patients,TERT promoter mutation rates in HBsAg negative and anti-HCV positive were significantly different(P<0.05).In addition,the difference in age,gender,tumor size,tumor number,vascular invasion,tumor differentiation,lymph node metastasis and TNM stage had no significance(P>0.05).Among RPC patients,TERT promoter mutation rates in lymph node metastasis and clinical stage were significantly different(P<0.05),and there was no significant difference in age,gender,smoking,tumor size and tumor differentiation(P>0.05).3.The postoperative median survival time of HCC patients with TERT promoter mutations was 39 months and that without TERT promoter mutations was 45 months,and there was no significant difference between two groups(P>0.05).The postoperative median survival time of RPC patients with TERT promoter mutations was 42 months and that without TERT promoter mutations was 56 months,and the difference between two groups were statistically significant(P<0.05).Multivariate Cox proportional hazards regression analysis showed that tumor differentiation,lymph node metastasis and TNM stage were the independent prognostic factors in patients with HCC(P<0.05),and TERT promoter mutations,clinical stage and tumor differentiation were independent prognostic factors in patients with RPC(P<0.05).Conclusion1.TERT promoter mutations occur frequently in HCC and RPC.2.TERT promoter mutations are associated with HBsAg negative and anti-HCV positive in HCC,and may provide novel and potential targets for antiviral treatment of HCV.3.TERT promoter mutations are associated with lymph node metastasis and clinical stages in RPC patients,and can influence the prognosis of RPC patients.TERT promoter may be a potential molecular therapeutic target in RPC.