原发性肝细胞癌组织中HSPG2蛋白的表达及其临床意义

Expression of HSPG2 in hepatocellular carcinoma and its clinical significance

目的探讨硫酸乙酰肝素糖蛋白(heparan sulfate proteoglycans,HSPGs)蛋白家族成员HSPG2在原发性肝细胞肝癌(hepatocellular carcinoma,HCC)中的过表达及其对临床诊断的价值与意义。方法采用免疫组化SP法检测70例HCC组织及相应癌旁组织中HSPG2、CD34的表达;采用Western blot法检测HSPG2蛋白的表达;收集30例原发性HCC患者、20例健康对照者血清样本,采用酶联免疫吸附试验(enzyme-linked immuno sorbent assay,ELISA)检测血清中HSPG2的水平,采用贝克曼UniCel Dx I800全自动免疫分析仪检测血清标本中AFP水平。结果 HSPG2蛋白在高、中、低分化HCC组中的微血管密度(microvessel density,MVD)值分别为22. 6、25. 3、29. 7,均高于相应癌旁组织(14. 7、14. 3、14. 6)(P <0. 05);平均光密度值(mean optical density,MOD)值分别为0. 540、0. 983、2. 068,均高于相应癌旁组织(0. 102、0. 100、0. 094)(P <0. 01)。这些数值与CD34标记的MVD与MOD值变化相一致。Western blot法检测发现HSPG2在HCC组织中的表达水平均明显高于癌旁组织(P <0. 01)。血清中HSPG2平均表达水平为1 078 ng/m L,高于健康对照组(536. 3 ng/m L),差异有显著性(P <0. 01);AFP平均表达水平为441. 0 ng/m L,明显高于对照组(3. 32 ng/m L)(P <0. 01)。结论 HSPG2表达升高与HCC恶化程度密切相关,提示其可能参与HCC的发生、发展,且在肝癌患者血清中显著增加,有作为肿瘤标志物的价值。

To investigate the overexpression of HSPG2,a member of heparan sulfate proteoglycans(HSPGs)protein family,in primary hepatocellular carcinoma(HCC)and its clinical significance.Method Immunohistochemistry was used to detect expression levels of HSPG2 and CD34 proteins in 70 cases of HCC tissues and corresponding para-cancer tissues.The expression of HSPG2 in 4 cases of HCC were detected by Western blot,sera from 30 primary HCC patients and 20 normal controls were collected and HSPG2 and AFP levels in serum were measured by ELISA and Beckman UniCel DxI800 access immunoassay system,respectively.Results As a major component of blood vessel basement membranes,microvessel density(MVD)values coupling with HSPG2 protein levels in well-,moderately-and poorly-differentiated HCC groups were 22.6,25.3,29.7,higher than that in adjacent tissues,which were 14.7,14.3,14.6,respectively(P<0.05).Mean optical density(MOD)values of HSPG2 labelling in well-,moderately-and poorly-differentiated HCC groups were 0.540,0.983,2.068,higher than that in adjacent normal tissues,which were 0.102,0.100,0.094(P<0.01).These variation trends were consistent with the changes of MVD and MOD values reflected by CD34 labelling.Compared with adjacent normal tissues,the expression of HSPG2 in HCC tissue increased apparently(P<0.01).The mean expression level of HSPG2 in sera of HCC group was 1 078 ng/mL,which was significantly higher than 536.3 ng/mL in the healthy control group(P<0.01).The mean expression level of AFP in sera of HCC group was 441.0 ng/mL,significantly higher than 3.32 ng/mL in the control group(P<0.01).Conclusion The increase of HSPG2 is closely related to the degree of deterioration of HCC,suggesting that HSPG2 may participate in the development of HCC.Furthermore,the increased levels of HSPG2 in sera from patients with HCC indicate its value as a tumor biomarker.