CD44和CD133在慢性乙肝和肝细胞癌患者组织中的表达及其临床意义

Expression and clinical significance of CD44 and CD133 in chronic hepatitis B and hepatocellular carcinoma

目的:研究CD44和CD133在HBV诱导的慢性肝病和肝细胞癌(HCC)患者肝组织中的表达,并评价其与炎症活动度、纤维化分期(慢性肝炎合并肝硬化或无肝硬化)及肝细胞癌分级的相关性。方法:选取2015年1月至2017年12月期间,我院收治的慢性乙肝未发生肝硬化的患者24例,慢性乙肝伴有肝硬化的患者24例和肝细胞癌患者24例,分为组Ⅰ、组Ⅱ、组Ⅲ,另收集病理肝脏组织正常,血清HBV抗体和HBsAg均为阴性的患者10例,根据METAVIR评分系统对非肿瘤性肝活检中的坏死性炎症活动度和纤维化分期进行评分,采用免疫组化SABC法检测CD44和CD133在各组中的表达水平。结果:各组中的CD44和CD133表达量均随疾病进展而显著增加,差异有统计学意义(P<0.05)。与A1F1评分相比,患者CD44和CD133的表达在炎症活动评分和纤维化达到A3F4评分时,有显著升高(P<0.05);且随肝细胞癌分级的升高,CD44和CD133的表达显著增加(P<0.05)。结论:在慢性肝炎、肝硬化和肝细胞癌中均有CD44和CD133的表达。CD44和CD133的表达与炎性活动、纤维化分期和肿瘤分级增加有显著相关性。因此肿瘤干细胞标记物CD44和CD133可以用于开发新的肝细胞癌靶向药物和预防性治疗药物。

Objective:To investigate the expression of CD44 and CD133 in patients with HCV-induced chronic liver diseases and hepatocellular carcinoma(HCC),and to evaluate the correlation with inflammatory activity,fibrosis stage(chronic hepatitis with cirrhosis or without cirrhosis)and grades of HCC.Methods:Totally,82 patients were collected in January 2015 to December 2017 and divided as fellows:GroupⅠ:24 patients with chronic hepatitis B without cirrhosis,GroupⅡ:24 patients with chronic hepatitis B with cirrhosis,GroupⅢ:24 patients with hepatocellular carcinoma,and 10 patients with serologically negative HBV-Ab and HBsAg,and histopathologically normal liver.Necroinflammatory activity and fibrosis in non-neoplastic liver biopsies were scored according to the METAVIR scoring system.Immunohistochemical SABC method was used to detect the expression levels of CD44 and CD133 in each group.Results:Our study showed that the expression of CD44 and CD133 increased significantly with the progression of disease(P<0.05).Compared with the A1F1 score,the expression of CD44 and CD133 in the patients increased significantly when the inflammatory activity score and fibrosis reached the A3F4 score(P<0.05).Moreover,the expression of CD44 and CD133 increased significantly with the increase of the grades of hepatocellular carcinoma(P<0.05).Conclusion:CD44 and CD133 are expressed in chronic hepatitis,cirrhosis and hepatocellular carcinoma.The expression of CD44 and CD133 was significantly correlated with inflammatory activity,fibrosis stage and higher tumor grades.Therefore,cancer stem cell markers CD44 and CD133 can be used to develop new targeted drugs and preventive drugs for hepatocellular carcinoma.