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凋亡和血管生成因子在评估肝细胞癌预后中的临床价值。

Clinical value of apoptosis and angiogenesis factors in estimating the prognosis of hepatocellular carcinoma.

作者信息

Guo Rong-Ping, Zhong Chong, Shi Ming, Zhang Chang-Qing, Wei Wei, Zhang Ya-Qi, Li Jin-Qing

机构信息

State Key Laboratory of Oncology in Southern China, 651 Dongfeng Road East, Guangzhou, 510060, China.

出版信息

J Cancer Res Clin Oncol. 2006 Sep;132(9):547-55. doi: 10.1007/s00432-006-0097-5. Epub 2006 Jun 9.

Abstract

PURPOSE

Whereas some studies have indicated that the prognosis of hepatocellular carcinoma (HCC) was correlated to some apoptosis and angiogenesis factors: p53, survivin, matrix metalloproteinases (MMPs, including MMP-2 and MMP-9) and vascular endothelial growth factor (VEGF), other studies have failed to confirm this. The aim of the present study is to investigate the expression of p53, survivin, MMPs and VEGF in HCC and the relationship between these factors and the prognosis of HCC patients.

METHODS

The expression of p53, survivin, MMP-2, MMP-9 and VEGF was measured by immunohistochemical assays in the liver resection specimens of 90 patients with HCC.

RESULTS

The positive rate of p53, survivin, MMP-2, MMP-9 and VEGF was 33.3, 51.1, 60.0, 37.8 and 76.7%, respectively. The expression of MMP-2, MMP-9 and VEGF was correlated to the recurrence of HCC patients, respectively (P < 0.01). No correlation was found between the expression of apoptosis factors (p53 and survivin) and the recurrence of HCC patients, respectively (P > 0.05). The positive correlations were found between MMP-2 and VEGF (r = 0.32, P < 0.01), MMP-9 and VEGF (r = 0.24, P < 0.05). Significant differences of disease-free survival rates occurred among subgroups according to the expression of MMP-2, MMP-9 and VEGF (P < 0.01). Multivariate analysis revealed that macroscopically disseminated nodules, tumor micrometastasis, high serum alpha-fetoprotein level, positive expression of MMP-9 and VEGF were independent recurrence risk factors.

CONCLUSIONS

Our investigation revealed that p53 and survivin could not estimate the prognosis of HCC patients. Angiogenesis factors (MMPs and VEGF) positively correlated to the prognosis of HCC patients. The expression of MMPs and VEGF in HCC tissues could be regarded as a valuable indicator in estimating the prognosis of HCC patients.

摘要

目的

虽然一些研究表明肝细胞癌(HCC)的预后与某些凋亡和血管生成因子相关,如p53、生存素、基质金属蛋白酶(MMPs,包括MMP - 2和MMP - 9)以及血管内皮生长因子(VEGF),但其他研究未能证实这一点。本研究的目的是调查p53、生存素、MMPs和VEGF在HCC中的表达情况以及这些因子与HCC患者预后之间的关系。

方法

采用免疫组织化学方法检测90例HCC患者肝切除标本中p53、生存素、MMP - 2、MMP - 9和VEGF的表达。

结果

p53、生存素、MMP - 2、MMP - 9和VEGF的阳性率分别为33.3%、51.1%、60.0%、37.8%和76.7%。MMP - 2、MMP - 9和VEGF的表达分别与HCC患者的复发相关(P < 0.01)。未发现凋亡因子(p53和生存素)的表达与HCC患者的复发之间存在相关性(P > 0.05)。发现MMP - 2与VEGF之间存在正相关(r = 0.32,P < 0.01),MMP - 9与VEGF之间存在正相关(r = 0.24,P < 0.05)。根据MMP - 2、MMP - 9和VEGF的表达情况,各亚组的无病生存率存在显著差异(P < 0.01)。多因素分析显示,肉眼可见的播散结节、肿瘤微转移、高血清甲胎蛋白水平、MMP - 9和VEGF的阳性表达是独立的复发危险因素。

结论

我们的研究表明,p53和生存素不能评估HCC患者的预后。血管生成因子(MMPs和VEGF)与HCC患者的预后呈正相关。HCC组织中MMPs和VEGF的表达可被视为评估HCC患者预后的一个有价值指标。

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