人醛氧化酶蛋白在肝癌中的表达及其临床意义

Expression of human aldehyde oxidase in hepatocellular carcinoma and its clinical significance

目的:探讨人醛氧化酶(human aldehyde oxidase,hAOX)蛋白在肝癌细胞系、肝癌组织、癌旁肝组织、肝硬化及正常肝组织中的表达及其临床意义。方法:采用Western印迹法和免疫组织化学法检测hAOX蛋白在7个肝癌细胞系、2个永生化肝细胞系、10例正常肝、12例肝硬化、57例肝癌及癌旁肝组织中的表达差异,分析其表达差异的临床意义。结果:Western印迹法检测结果表明,hAOX蛋白在MHCC-LM3、Hep3B、Huh-7和BEL-7402肝癌细胞系以及人永生化肝细胞系L-02和Chang’s liver等6个细胞系中均有较高表达,在MHCC-97L、HepG2和SMMC-7721细胞中则为低表达。免疫组织化学检测发现,hAOX在正常肝、肝硬化组织和癌旁肝组织中高表达,在癌旁肝组织中的表达较匹配肝癌组织的高(P<0.001)。Western印迹法检测结果提示癌旁肝组织中hAOX表达明显高于肝癌组织。hAOX表达与肝癌患者性别、年龄、血清甲胎蛋白(alpha-fetoprotein,AFP)水平、乙肝表面抗原、肿瘤大小、病理学分级以及是否伴有肝硬化均无相关性(P>0.05),而与肿瘤血管侵犯和肿瘤生长方式有一定的相关性(P=0.053,P=0.011)。结论:hAOX在正常肝、肝硬化、癌旁肝组织中高表达,而在肝癌组织中表达明显降低,其表达可能会影响肝癌的血管侵犯和肿瘤生长方式。

Objective：To explore the differential expression and significance of human aldehyde oxidase （hAOX） in hepatocellular carcinoma （HCC） cell lines, primary HCC tissues, pericancerous tissues, cirrhotic liver tissues as well as normal liver tissues. Methods： Western blot and immunohistochemical method were used to detect the differential expression of hAOX protein in 7 HCC cell lines, 2 immortalized hepatic cell lines, 10 cases of normal liver tissues, 12 cases of cirrhotic liver tissues, 57 cases of pericancerous liver tissues and matched primary HCC tissues. Its clinical pathological significance was statistically analyzed by SPSSI6.0 software. Results： Western blot analysis showed that hAOX protein was highly expressed in MHCC-LM3, Hep3B, Huh-7, and BEL-7402 HCC cells and immortalized hepatic cell lines L-02 and Chang＇ s liver; it was moderately expressed in MHCC-97L, HepG2 and SMMC-7721 cell lines. IHC detection showed that hAOX protein was over-expressed in normal liver, cirrhotic liver and pericancerous liver tissues. It was significantly higher in pericancerous liver tissues than that in the matched HCC tissues （ P 〈 0. 001 ）, which was confirmed by Western blot. Statistical analysis showed that hAOX protein expression had no association with gender, age, serum AFP level, HBsAg, tumor size, pathological grade and with or without liver cirrhosis of HCC patients （ P 〉 0.05 ）. It was related with portal invasion and tumor growth patterns to some extent （ P = 0. 053, P = 0.011 ）, in which hAOX positive staining was significantly related to tumor invasire growth pattern （P 〈 0. 05 ）. Conclusion： hAOX protein was over-expressed in normal liver, cirrhotic liver and pericancerous liver tissues, and weakly expressed in the matched HCC tissues. The expression of hAOX may affect tumor vascular invasion and growth patterns.