CAS基因在原发性肝癌组织中的表达及其与HBV感染的关系

Expression of CAS in hepatocellular carcinoma tissues and its relationship with HBV infection

目的探讨细胞凋亡易感基因（CAS）可否作为肝癌的病理诊断标志物，以及肝细胞癌中CAS蛋白的表达与HBV感染之间的关系。方法应用免疫组化法检测肝癌、癌旁组织及未发生肿瘤的肝硬化、肝炎组织中CAS蛋白的表达情况，同时应用免疫组化法、核酸原位杂交法检测HBV感染的肝细胞癌组织、癌旁组织中HBsAg、HBcAg以及HBVDNA的表达情况，分析肝细胞癌中CAS蛋白的表达与HBV感染之间的关系。结果CAS蛋白在肝癌组织中的表达较癌旁组织明显升高（P〈0．01），而癌旁组织中CAS蛋白表达较未发生肿瘤的肝硬化、肝炎组织显著增强（P〈0．01）。低分化型肿瘤细胞的CAS蛋白表达明显高于中分化型和高分化型（P〈0．01）。CAS蛋白在HBV感染的肝细胞癌组织中的表达明显高于非HBV感染的癌组织（P〈0．01），其中HBVDNA阳性的肝细胞癌组织中CAS蛋白表达水平显著高于HBVDNA阴性的肝细胞癌组织（P〈0．05）。结论CAS蛋白在肝细胞癌组织中呈高表达，肝细胞癌分化愈低其表达愈强，表明CAS蛋白可作为肝细胞癌的病理诊断与分化程度的评价标志物。并推测HBVDNA可能通过上调CAS的表达，在HBV感染相关性肝癌的发生发展过程中发挥重要的作用。

Objective To explore whether the cellular apoptosis susceptibility （CAS） protein could serve as a pathologic marker for HCC diagnosis and the roles of CAS expression in HBV infection associated HCC. Methods The expression of CAS protein in HCC and its paracarcinoma tissues, non-tumor liver cirrhosis and hepatitis tissues were detected by immunohistochemistry. Meanwhile, HBsAg, HBcAg and HBV DNA in HCC tissues with HBV infection were examined by immunohistochemistry and in situ hybridization respectively. Results The expression of CAS protein was significantly higher in HCC than in its paracareinomas tissues （P 〈 0. 01 ）, apd higher in paracarcinomas tissues than in non-tumor liver cirrhosis and hepatitis tissues （ P 〈 0.01 ）. Poorly differentiated tumors immunochemically＇ stained stronger than moderately or well differentiated（ P 〈 0. 01 ）. CAS protein expression was significantly higher in HBV- infected HCC tissues than that of in non-HBV infection （P 〈 0. 01 ）. Meanwhile, in HBV-infected HCC tissues, the staining intensity score of CAS protein in HBV DNA positive HCC tissues was significantly higher than HBV DNA negative tissues （ P 〈 0. 05）. Conclusions Higher expression of CAS protein is found in HCC tissues,and the intensity of CAS protein expression is related closely to tumor differentiation. We suggested that CAS protein might serve as a marker for HCC diagnosis and differentiation estimation,and deduced that CAS might play an important role in the initiation of HBV infection associated HCC through upregulating expression of CAS.