| Objective:To analyze the expression levels of the mRNA and protein of the telomeric repeat binding factor (TRF)1and2to telomere binding proteins in hepatocellular carcinoma tissue, and to evaluate the relationship of the expression levels of the mRNA and protein of TRF-1and TRF-2and clinical pathological parameters, and to investigate the role of TRF-1and TRF-2in the occurrence and development of hepatocellular carcinoma, in order to providing the theoretical evidence to telomeric regulatory networks to diagnosis and treatment of hepatocellular carcinoma.Methods:A total of60patients with hepatocellular carcinoma received operation in general surgery department from January2012to August2013were chosen to research objects.The male patients were42cases and female were18cases. And the age range in all patients was from38years to62years and the mean age was (57.6±14.3) years. The selection criterias of this research were the below items:①The surgical specimens were pathological diagnosis after operation.②All patients were never received the chemotherapy and radiotherapy before operation.③All patients signed the information consent form. The resection samples of hepatocellular carcinoma tissue were collected to hepatocellular carcinoma group, and the liver tissure of the same patient which the locations were more than5cm from the edges of cancer tissure were collected to pericarcinomatous tissue group. The10patients which received liver biopsy and exclude the diagnosis of hepatocellular carcinoma in our hospital at the corresponding period were chosen and the liver tissure of these patients were collected to normal tissue group. Follow-up half year, the cases of postoperative recurrence (including the local recurrence and distant metastasis) and the death were recorded in two groups, then the recurrence ratio and mortality rate were calculated.(1) The analysis of normal clinical baseline indexes. The differences of normal clinical baseline indexes were compared between hepatocellular carcinoma patients and non-hepatocellular carcinoma patients, including age, gender ratio, body mass index (BMI), AFP level, HBsAg positive ratio and mortality rate.(2) The analysis of the expression level of TRF1and TRF2protein. The expression levels of TRF1and TRF2protein in hepatocellular carcinoma specimen tissure among three groups were detected by immunohistochemistry Streptavidin-perosidase (S-P) method.The relationships of normal clinical baseline indexes (age, gender ratio, BMI, AFP level, HBsAg positive ratio) and clinical pathological parameters (tumor volume, tumor number, portal vein carcinoma thrombosis rate, capsule integrity rate and pathological classification) to the expression level of TRF1and TRF2protein were analyzed.(3) The correlation analysis of the indexes to the occurrence of the tumor cell metastasis rate. The correlation analysis of the normal clinical baseline indexes and the clinical pathological parameters and the expression levels of the protein of TRF-1and TRF-2to the occurrence of the tumor cell metastasis rate were analyzed by Pearson correlation coefficient.(4) The analysis of the risk factors to the occurrence of the tumor cell metastasis rate. The hazard level of the normal clinical baseline indexes and the clinical pathological parameters and the expression levels of the protein of TRF-1and TRF-2to the occurrence of the tumor cell metastasis rate were analyzed by multivariate COX proportional hazard model.Results:(1) The comparison of normal clinical baseline indexes. Compared to non-hepatocellular carcinoma patients, the indexes of age, gender ratio, body mass index (BMI) in hepatocellular carcinoma patients were no different (all P>0.05), but the indexes of AFP level, HBsAg positive ratio and mortality rate in hepatocellular carcinoma patients were higher (all P＜0.05).(2) The comparison of the expression level of TRF1and TRF2protein.The expression levels of TRF1and TRF2protein were detected in normal tissue group, hepatocellular carcinoma group and pericarcinomatous tissue group. The expression levels of TRF1protein were80.0%(8/10),46.7%(28/60) and85.0%(51/60), respectively, and the expression levels of TRF2protein were30.0%(3/10),90.0%(54/60) and28.3%(17/60), respectively.The expression levels of TRF1protein in hepatocellular carcinoma group were obviously lower than normal tissue group and pericarcinomatous tissue group (P<0.05), but the expression levels of TRF1protein were no different between normal tissue group and pericarcinomatous tissue group (P>0.05). The expression levels of TRF2protein in hepatocellular carcinoma group were obviously higher than normal tissue group and pericarcinomatous tissue group (P＜0.05), but the expression levels of TRF1protein were no different between normal tissue group and pericarcinomatous tissue group (P>0.05).The expression levels of TRF1and TRF2protein were no relationship to the indexes of age, gender ratio, BMI, AFP level, HBsAg positive ratio, tumor volume and tumor number in hepatocellular carcinoma patients (P>0.05), but the relationships were comfirmed among the expression levels of TRF1and TRF2protein to the indexes of portal vein carcinoma thrombosis rate, capsule integrity rate and pathological classification (P<0.05).(3) The correlation analysis of the indexes to the occurrence of the tumor cell metastasis rate. The positive correlations of the indexes of portal vein carcinoma thrombosis rate, capsule integrity rate and pathological classification, the expression level of TRF2and the occurrence of the tumor cell metastasis rate were confirmed by Pearson correlation coefficient (all P<0.05). But the negative correlations of the expression level of TRF2and the tumor volume and the occurrence of the tumor cell metastasis rate were confirmed by Pearson correlation coefficient (all P<0.05). There were no correlations of the indexes of age, gender ratio, body mass index (BMI), AFP level, HBsAg positive ratio and tumor number and the occurrence of the tumor cell metastasis rate were confirmed by Pearson correlation coefficient (all P>0.05).(4) The analysis of the risk factors to the occurrence of the tumor cell metastasis rate.The risk factors to the occurrence of the tumor cell metastasis rate were pathological differentiated degree, capsule integrity, the expression levels of the protein of TRF-1and TRF-2confirmed by multivariate COX proportional hazard model (all P<0.05).Conclusion:(1) The expression levels of the protein of TRF-1and TRF-2in hepatocellular carcinoma tissue were changing obviously, and the down-regulation of the expression levels of TRF1gene and up-regulation of the expression levels of TRF2gene both could improve the occurrence and development of hepatocellular carcinoma.(2) The expression levels of the protein of TRF-1and TRF-2were the risk factors to the occurrence of the hepatocellular carcinoma metastasis and could be judge the prognosis of colon carcinoma. |
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