信号调节蛋白与肝癌相关性的研究

The association between signal regulatory protein α and hepatocellular carcinoma

目的研究信号调节蛋白ＳＩＲＰα与肝细胞肝癌的发生及侵袭之间的联系。方法应用Ｎｏｒｔｈｅｒｎ杂交及免疫组织化学技术检测了４２对肝细胞肝癌和相应癌旁肝组织内ＳＩＲＰα基因表达的变化，并结合各组织标本的病理学特点进行分析。结果ＳＩＲＰα的３．９ｋｂ转录子及２．５ｋｂ转录子分别在２１例、２７例肝癌组织内表达水平明显下降。直径＞５ｃｍ的大肝癌ＳＩＲＰα的表达下降率显著高于直径≤５ｃｍ的小肝癌，有癌栓形成的肝癌ＳＩＲＰα的表达下降率显著高于无癌栓的肝癌。ＳＩＲＰα的表达下降与患者年龄、肿瘤分级、包膜完整性、血清ＡＦＰ水平、是否有乙肝感染无明显相关性。免疫组织化学显示在正常肝细胞、胆管上皮细胞、Ｉｔｏ细胞、再生肝细胞、新生胆管细胞及部分肝细胞肝癌（ＨＣＣ）细胞均有表达。表达下降的ＨＣＣ细胞表现为阳性颗粒变淡、变少，部分ＨＣＣ细胞或区域完全无染色。结论ＳＩＲＰα尤其是２．５ｋｂ转录子在肝癌内表达下降，与肝癌的生长、侵袭密切相关，可能为肝癌发生发展过程中一个重要的负调控因子。

Objective To study the roles of signal regulatory protein α (SIRPα) in the development of hepatocellular carcinoma (HCC). Methods 42 pairs of HCC and the surrounding noncancerous hepatic tissues were used . The expression of SIRPα in various tissues was determined by Northern blot analysis and immunohistochemistry assay, by which together with the pathologic characteristics of each sample, the role of SIRPα was investigated. Results The expression of SIRPα significantly decreased in 21 cases of samples (50.0%) to the 3.9kb transcript and 27 cases of samples (64.3%) to the 2.5kb transcript respectively. The SIRPα decreasing rate in large HCC(>5cm in diameter)was higher than in small HCC (≤5cm in diameter) , and in HCC with cancer embolus was higher than that of without cancer embolus . No association was found between the SIRPα expression and the patient's age, tumor grade, tumor capsule, serum AFP level, and HBV infection. Immunohistochemistry showed that all the normal hepatocytes, cholangioepithelial cells, Ito cells, regenerated hepatocytes, new generated cholangioepithelial cells and part of HCC cells were positive. The HCC tissues in which SIRPα was down regulated showed positive particles becoming weaker and less, and some tumor cells and area were completely negative. Conclusion The expression of SIRPα especially 2.5kb transcript is down regulated in HCC, which is closely related with the tumor growth and invasiveness. SIRP α may be an important negative regulator of HCC.