血管生成因子AGGF1表达与肝细胞癌患者预后的关系

Predictive value of angiogenic factor AGGF1 for prognosis in patients with hepatocellular carcinoma

目的 :探讨肝细胞癌(HCC)患者肿瘤组织中血管生成因子AGGF1表达与肿瘤血管生成及HCC患者预后的相关性。方法:通过免疫组织化学方法检测183例HCC与癌旁组织中AGGF1蛋白的表达、癌组织中血管内皮生长因子(VEGF)和微血管密度(MVD),比较AGGF1蛋白表达与VEGF和MVD的相关性,探讨AGGF1蛋白表达与HCC患者无进展生存期(PFS)和总体生存期(OS)的相关性。结果:183例HCC癌组织中AGGF1阳性率显著高于癌旁组织(68.3%比14.2%,P<0.001)。与AGGF1阴性组(58例)相比,AGGF1阳性组(125例)中多发肿瘤患者更多(13.6%vs 0.0%,P=0.003)、TNMⅢ~Ⅳ期患者更多(46.4%比25.9%,P=0.008)和BCLC分级为B级患者更多(57.6%比31.0%,P=0.001)。AGGF1阳性组的VEGF染色阳性率显著高于AGGF1阴性组(71.2%比22.4%,P<0.001),MVD也显著高于AGGF1阴性组患者(32.6±8.4比16.5±5.5,P<0.001)。Kaplan-Meier生存曲线证实AGGF1阳性患者的PFS和OS均显著短于AGGF1阴性患者(P<0.001)。单因素及多因素Cox回归分析证实,TNMⅢ-Ⅳ期、AGGF1阳性是影响HCC患者OS的独立危险因素。结论:AGGF1蛋白水平是影响HCC患者术后OS的独立危险因素,提示AGGF1蛋白可作为HCC患者的预后有效标志物。

Objective:To investigate the predictive value of angiogenic factor AGGF1 and tumor angiogenesis for prognosis in patients with hepatocellular carcinoma(HCC).Methods:The expression of AGGF1,vascular endothelial growth factor(VEGF)and microvessel density(MVD)were detected by immunohistochemistry in cancerous and paracancerous tissues of 183 patients with HCC.The association between AGGF1 expression and VEGF and MVD were compared,and the correlation between AGGF1 expression and progression-free survival(PFS)and overall survival(OS)was assessed in HCC patients.Results:The positive rate of AGGF1 in cancerous tissues was significantly higher than that in paracancerous tissues(68.3%vs 14.2%,P<0.001).Compared with the AGGF1-negative group(n=58),the AGGF1-positive group(125 patients)had more patients with multiple tumors(13.6%vs 0.0%,P=0.003),TNMⅢ-Ⅳ(46.4%vs 25.9%,P=0.008)and grade B of BCLC grade(57.6%vs 31.0%,P=0.001).The positive rate of VEGF staining in AGGF1-positive group was significantly higher than that in AGGF1-negative group(71.2%vs 22.4%,P<0.001),and MVD was also significantly higher than that in AGGF1-negative group(32.6±8.4 vs 16.5±5.5,P<0.001).Kaplan-Meier survival analysis confirmed that both PFS and OS in AGGF1-positive patients were significantly shorter than those in AGGF1-negative patients(P<0.001).Univariate and multivariate Cox regression analysis confirmed that TNM stage Ⅲ-Ⅳ,AGGF1 positive were both independent risk factors for worse OS in patients with HCC.Conclusion:AGGF1 expression is an independent risk factor for postoperative OS in patients with HCC,which could be used as a effective prognostic marker for HCC patients.