【目的】脾酪氨酸激酶(SYK)有两种蛋白异构体的存在,全长型SYK(L)和缩短型SYK(S),两者在恶性肿瘤中功能不同;肝癌中SYK(L)功能未见报道。本研究通过定制的SYK(L)特异性多克隆抗体,检测其在肝细胞癌组织中的表达,探讨SYK(L)表达与肝癌患者临床病理因素及预后关系。【方法】定制SYK(L)的特异性抗体,采用免疫组化方法检测162例肝癌患者的肿瘤组织及其癌旁肝组织SYK(L)蛋白的表达情况,分析其与临床病理因素及患者术后生存的关系。【结果】定制SYK(L)抗体的特异性良好;肝癌组织中SYK(L)阳性率为64.8%(105/162),低于癌旁肝组织98.1%(159/162)(P〈0.001);SYK(L)表达与肿瘤大小、肿瘤分化程度、有无卫星结节和血管侵犯相关(P〈0.05)。肿瘤中SYK(L)蛋白阳性表达肝癌患者的术后无复发生存与总体生存明显长于阴性表达者(P〈0.001)。多因素Cox回归模型显示,SYK(L)表达状态是肝癌患者无复发生存期与总体生存期的独立危险因素之一(P〈0.001)。【结论】肝癌组织中SYK(L)蛋白表达减低,与肿瘤分化、侵袭转移和预后相关;SYK(L)可作为判断肝癌患者预后的有效分子标志物。
[Objective] Spleen tyrosine kinase(SYK) has two isoforms,full-length form SYK(L) and short form SYK(S),which has different roles in human malignant tumor.The reports of SYK(L) in HCC are few.This study was to generate SYK(L)-specific antibody,and investigate the correlation between the expression pattern of SYK(L) protein in HCC and clinicopathological characteristics and prognosis.[Methods] SYK(L)-specific antibody was generated by a biotech company.The expression of SYK(L) was detected in 162 cases of HCC tissues and adjacent non-tumor liver tissues by immunohistochemistry.The relationship between the expression statues of SYK(L) and clinicopathological characteristics and prognosis was analyzed.[Results] The specificity of SYK(L)-specific antibody(SYK-23) was well.The positive rate of SYK(L) was significantly lower in HCC tissues [64.8%(105/162)] than that in adjacent non-tumor tissues [98.1%(159/162)](P 0.001);moreover,SYK(L) expression was significantly associated with the tumor size,tumor differentiation,satellite nodule and vascular invasion(all P 0.05).After resection of primary HCC,the patients with SYK(L)-positive tumors had a significant longer recurrence-free survival(RFS) and overall survival(OS) than those with SYK(L)-negative tumors.The multivariate cox proportional hazards regression analysis of prognostic factors for RFS and OS showed that the expression of SYK(L) was an independent factor for prognosis of HCC.[Conclusion] Down-regulation of SYK(L) protein expression may be involved in the carcinogenesis and metastasis of HCC,and is a powerful molecular marker to predict the HCC prognosis.