VEGF与MMP-9在肝癌组织中的表达及其临床意义

背景与目的：血管内皮生长因子vascular endothelial growth factor,VEGF）及基质金属蛋白酶-9（matrix metalloproteinase-9,MMP-9）与恶性肿瘤的侵袭、血管生成及预后有一定关系。VEGF与MMP-9表达对预测肝细胞癌（以下简称“肝癌”）患者预后的报道结果不一。本研究旨在探讨VEGF与MMP-9在肝癌组织中的表达及其预测肝癌患者预后的意义。方法：按是否复发将80例肝癌患者分为复发组与未复发组,采用免疫组化方法检测两组手术切除标本中VEGF及MMP-9的表达情况,分析两者的表达与临床病理指标的关系。建立Cox比例风险模型进行肝癌术后复发风险的多因素分析。结果：MMP-9及VEGF表达于肿瘤细胞浆中,复发组的阳性率分别为50．0％（24／48）及87．5％（42／48）,未复发组分别为15．6％（5／32）及59、4％（19／32）,差异均有显著性（P〈0．05）。VEGF与MMP-9的表达呈正相关（rs=0．36,P〈0．01）,并均与复发呈正相关（P〈0．01）。VEGF阴性患者的1、2、3年累积无瘤生存率分别是85．7％、71．4％及66．3％,VEGF阳性患者分别为58．0％、38．9％及33．9％,差异有显著性（P〈0．01）;MMP-9阴性组分别为72．4％、63．8％及55．5％,MMP-9阳性组分别为50．0％、14．1％及14．1％,差异有显著性（P〈0．01）。多因素分析发现,肝癌组织中VEGF和MMP-9的表达、术前播散结节及镜下微转移灶是肝癌术后复发的独立危险因素。结论：肿瘤组织中VEGF及MMP-9的表达与肝癌患者的术后复发密切相关,为预测肝癌患者术后复发的指标之一。

Expression and clinical significance of VEGF and MMP-9 in hepatocellular carcinoma

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are related to invasiveness, angiogenesis, and prognosis of malignancies. However, the reports on the results of VEGF and MMP-9 in estimating the prognosis of hepatocellular carcinoma (HCC) patients are different. This study was to investigate the expression and clinical value of VEGF and MMP-9 in HCC patients. METHODS: The expression of MMP-9 and VEGF in 80 specimens of HCC was detected by immunohistochemistry. Of the 80 patients, 48 had tumor recurred within 2 years after operation. Correlations of the expression of MMP-9 and VEGF to clinicopathologic features were analyzed. Cox regression model was used to analyze the recurrence risk factors after hepatectomy. RESULTS: MMP-9 and VEGF were expressed in cytoplasm. The positive rates of MMP-9 and VEGF were significantly higher in recurrent group than in non-recurrent group (50.0% vs. 15.6%, and 87.5% vs. 59.4%, P<0.05). The expression of MMP-9 was positively correlated to that of VEGF (rs=0.36, P<0.01), and both were positively correlated to recurrence of HCC(P<0.01). The 1-, 2-, and 3-year tumor-freely survival rates were significantly higher in VEGF-negative group than in VEGF-positive group (85.7% vs. 58.0%, 71.4% vs. 38.9%, and 66.3% vs. 33.9%, P <0.01), and were significantly higher in MMP-9-negative group than in MMP-9-positive group (72.4% vs. 50.0%, 63.8% vs. 14.1%, and 55.5% vs. 14.1%,P <0.01). Multivariate analysis revealed that preoperative disseminated nodules, tumor micrometastasis, and the expression of MMP-9 and VEGF were independent recurrence risk factors. CONCLUSION: The expression of MMP-9 and VEGF in HCC tissues is closely correlated to the recurrence of HCC after hepatectomy, and could be used to estimate the risk of postoperative recurrence of HCC.