The Association Of ?-taxilin With Hepatocellular Carcinoma Prognosis As Well As The Interaction Between ?-taxilin And HBV

Objective: Hepatocellular carcinoma(HCC)is one of the most prevalent malignancies in the world,accounting for 70%-90% of primary liver cancer.By 2012,it became the fifth most common cause of cancer in men and ninth in women,with approximately 554,400 and 228,100 new cases,respectively.Liver cancer ranked second in men,and sixth in women,in estimated mortality.The most common risk factors that have been associated with the development of HCC are chronic hepatitis B/C virus(HBV/HCV)infection,excessive alcohol and aflatoxin consumption,of these,HBV is the major risk factor for HCC.About 54.4% of HCC cases are attributed to HBV infection.A considerable number of the patients with chronic hepatitis B slowly developed into hepatic cirrhosis,and then developed into the HCC,which seriously threat to the health of the people of our country and consume a large amount of medical resources.Despite improved clinical detection methods and therapies for HCC,include hepatectomy,transcatheter arterial chemoembolization(TACE),radiofrequency ablation(RFA),radiotherapy and chemotherapy and targeted therapy,the prognosis of the patients with postoperative HCC is still poor because of a high recurrence rate and a high metastatis rate.Membrane transport system has been recognized to be involved in carcinogenesis and tumor progression in several types of tumors.?-taxilin is one of the isoforms of taxilin family and a novel membrane traffic-related molecule.The structure of ?-taxilin is characterized by a long coiled-coil domain and a leucine zipper motif.?-taxilin is involved in post-Golgi vesicle trafficking through binding with syntaxin family.Moreover,?-taxilin is involved not only in the transcriptional and translational process through its interaction with the nascent polypeptide-associated complex(NAC),but alsoin the recycling pathway of TfnR through its interaction with sorting nexin4(SNX4).It is considered that ?-taxilin plays an important role in cell proliferation,differentiation,HBV DNA particle release and Ca2+-dependent exocytosis in neuroendocrine cells.In addition,?-taxilin is expressed in proliferating neuroepithelial cells and neural stem cells during murine embryonic development,it also expressed in dividing gastrointestinal epithelial cells during murine postnatal development.Previous reports showed that ?-taxilin overexpressed in hepatocellular carcinoma,renal cell carcinoma and gliomas,but its physiological function and the mechanism of influencing tumor development remained not clear.In this research,we used immunohistochemical method to measure the protein expression of ?-taxilin in HCC tissues so as to assess its effect on the prognosis of HCC as well as the interaction between ?-taxilin and HBV.Our results will helpful for prediction and prevention of HCC.Methods:1 Immunohistochemical SP methods were used to measure the protein expression of ?-taxilin in 58 cases of HCC tumor tissues.2 The survival data were analyzed by the Kaplan-Meier method,differences were determined by the log-rank test and the prognostic significance of clinical characteristics was assessed by the multivariate Cox proportional hazard model.Differences in clinical characteristics between the high and low ?-taxilin expression groups were compared with the ?2 test.P<0.05 was considered to be statistically significant and all calculations were performed using SPSS 21.0 software.Results:1 Univariate analysis of the clinical characteristics associated with postoperative survival in HCC patients: Gender,age,tumor number,Child-Pugh classification and HBV DNA copy number were not statistically significant predictors of postoperative survival time by Kaplan-Meier analysis(P>0.05);however,tumor size,portal vein thrombosis and TNM classification were significantly associated with the survival time(P<0.05).2 Association of the ?-taxilin expression with the prognosis of HCC patients: the ?-taxilin expression was significantly associated with HCC survival time by Kaplan-Meier analysis(P=0.007),patients with the low?-taxilin expression group displayed a longer survival time compared to patients with the high ?-taxilin expression group.3 Multivariate analysis of prognosis factors for HCC patients: Portal vein thrombosis and the ?-taxilin expression were identified as independent predictors for prognosis of HCC by Cox proportional hazards model(RR,3.069;95%CI,1.037-9.086;P=0.043 vs RR,0.386;95%CI,0.162-0.919;P=0.031).4 Association of the ?-taxilin expression with clinical characteristics in HCC patients: Gender,age,tumor size,tumor number,portal vein thrombosis,Child-Pugh classification and TNM classification were not significantly associated with the ?-taxilin expression by ?2 test,however,HBV DNA copy number correlated positively with the ?-taxilin expression(r=0.365,P=0.005).Conclusion:1 we proved that the ?-taxilin expression was associated with HCC survival time as an independent predictor of prognosis of HCC.2 The ?-taxilin expression correlated positively with HBV DNA copy number.