Expression And Significance Of Hic-5 In Hepatocellular Carcinoma

Ojective: Hepatocellular carcinoma(HCC)is the sixth most prevalent malignant tumors in the world.HCC has a strong invasiveness,and the possibility of recurrence and metastasis after surgical resection is still very large.It is of great significance to study the mechanism of the occurrence,progression and invasion of HCC,with the purpose of reducing its incidence and mortality.We detected the expression of hydrogen peroxide-inducible clone-5(Hic-5)and α-smooth muscle actin(a-SMA)in the HCC and normal liver tissues,in order to investigate the relationship between Hic-5,a-SMA and the occurrence,progression of HCC,and the underlying mechanism.In addition,we analysed the correlation between the expression of Hic-5,a-SMA and clinicopathological features of HCC patients.Methods:This experiment was approved by the ethics committee of hospital and all patients were gave informed consent.67 cases of HCC liver tissues and corresponding paracancerous liver tissues were obtained after surgical resection,including 22 cases in high differentiated group,24 cases in middle differentiated group and 21 cases in poorly differentiated group.Meanwhile,15 normal liver tissues around hepatic hemangioma after surgical resection were taken as normal control group.We applied immunohistochemistry(IHC)and western blot(WB)to detect the expression of Hic-5 and a-SMA in the normal liver tissues of the control group,HCC liver tissues and corresponding paracancerous liver tissues with different differentiation grades.We applied Image pro plus 7.0 software to deal with the results of IHC by collecting the optical density value of Hic-5 and a-SMA.The results of WB were processed with Gel imaging analysis system,and Quantity One 5.4 software was used to measure grey level of each band.The clinical data of each patient was collected simultaneously,including hospital ID,gender,age,preoperative imaging examinations,blood routine examination,blood coagulation function test,liver function test,renal function test,markers of hepatitis virus and serum alpha-fetoprotein.The postoperative pathological data of tumors was also collected subsequently,including tumor number,size,degree of differentiation,vascular invasion,regional lymph node metastasis,TNM staging and background of liver cirrhosis.The experimental data was processed and analyzed by using a statistical software,SPSS 17.0.Measurement data were expressed as mean±standard deviation(?x±s).The statistical analysis methods used in this experiment included Independent-Samples T Test,one way Analysis of Variance(ANOVA),Least Significant Difference T Test or Kruskal-Wallis Test.The correlation between variables was analyzed by linear correlation coefficient or Spearman rank correlation.Differences were considered statistically significant at P value <0.05.Results:1.IHC results:In liver tissues of the control group,Hic-5 did not expressed or expressed weakly only in hepatic lobule portal area.Hic-5 in HCC liver tissues and corresponding paracancerous liver tissues stained mainly in tumor stroma,including hepatic sinus,fibrous septum or capsule surrounding HCC cells.The intensity of Hic-5 expression(optical density value)was gradually increased with the decrease of differentiation of HCC.The intensity of Hic-5 expression in HCC group was higher than corresponding paracancerous group and control group.a-SMA in liver tissues of the control group stained rarely in hepatic lobule portal area.In HCC liver tissues,the expression of a-SMA coincided with Hic-5,also stained mainly in tumor stroma,including hepatic sinus,fibrous septum or capsule surrounding HCC cells.The intensity of a-SMA expression was similarly and gradually increased with the decrease of differentiation of HCC.The intensity of Hic-5 and a-SMA expression in HCC group were both higher than corresponding paracancerous group and control group.In the paracancerous liver tissues with a background of cirrhosis,the expression of Hic-5 and a-SMA were both higher than liver tissues without cirrhosis or liver tissues in control group.2.WB results:The intensity of Hic-5 and a-SMA protein expression(grey level)in HCC group were both higher than corresponding paracancerous group and control group.In the same manner,with the decrease of differentiation of HCC,The intensity of Hic-5 and a-SMA protein expression were also gradually increased.Meanwhile,in the HCC group and corresponding paracancerous group,the expression of Hic-5 protein and a-SMA protein were correlated.3.Analysis of clinical and pathological characteristics of patients with HCC indicated that the expression level of Hic-5 and a-SMA protein were related to the number of tumors,the degree of differentiation,vascular invasion,TNM staging and the background of cirrhosis.The patients? gender,age,regional lymph node metastasis,liver function grade,markers of hepatitis virus and serum alpha fetal protein were independent.Conclusions:1.Compared with the liver tissues in the control group and paracancerous group,Hic-5 and a-SMA were highly expressed in HCC liver tissues.It indicated that the expression of Hic-5 and a-SMA was related to the occurrence of HCC.2.In HCC liver tissues,with the decrease of differentiation of HCC,the intensity of Hic-5 and a-SMA expression were gradually increased.It indicated that Hic-5 and a-SMA might be involved in the occurrence and progression of HCC.3.The expression of Hic-5 was positively correlated with a-SMA in each group,and the IHC results revealed that Hic-5 and a-SMA both stained mainly in tumor stroma,suggesting there might be a synergistic or regulatory effect between Hic-5 and a-SMA in the occurrence and progression of HCC.The underlying mechanism might be to participate in the occurrence and progression of HCC by activating hepatic stellate cell.4.The study of clinical and pathological features of patients with HCC revealed Hic-5 and a-SMA protein might affect the number of tumors,differentiation,vascular invasion and background of cirrhosis to participate in the occurrence and progression of HCC.