c-met 蛋白在胃癌中的过表达及 uPAR 作为治疗靶点的作用。

Overexpression of c-met Protein in Gastric Cancer and Role of uPAR as a Therapeutic Target.

出版信息

Cancer Res Treat. 2003 Feb;35(1):9-15. doi: 10.4143/crt.2003.35.1.9.

DOI:10.4143/crt.2003.35.1.9

Abstract

PURPOSE

One of the members of the tyrosine kinase receptor family is the protein product of the c-met proto-oncogene, which is the receptor for hepatocyte growth factor (HGF). HGF is known as a potent mitogen and motogen for many kinds of carcinoma cells, and has been found to simulate the growth and progression of gastric cancer cells through HGF-receptors. In addition, the urokinase-type plasminogen activator (uPA) and receptor (uPAR) also play important roles in the invasion and metastasis.

MATERIALS AND METHODS

The expression of c-met protein was investigated using immunohistochemical staining of 50 paraffin embedded gastric cancers, and by measuring the serum uPAR levels, before and after an operation, in gastric cancer patients using an ELISA assay.

RESULTS

Of the 50 cases, 32 (64%) expressed the c-met protein. The c-met protein expression was significantly correlated with the TNM staging (p<0.05), but the other prognostic factors were not significant variables. According to a Kaplan-Meier's plot, the one and three year overall survival rates were 94 and 70% in patients not expressing the c-met protein, and 81 and 33% in those that did, and the Survival curves revealed a significantly different prognosis (p=0.04). Elevated serum uPAR levels (> or=3257.8 pg/ml, control+/-mean 2SD) were observed in 9 (34.6%) of 26 gastric cancer patients, but in none of control subjects. Average serum uPAR levels were 2980.8+/-616.2 pg/ml before the operation and 2404.7+/-455.9 pg/ml after, and decreased significantly after surgical resection (p<0.05). The serum uPAR level correlated significantly with lymph node metastasis and vessel invasion (p<0.05).

CONCLUSION

The expression of c-met protein, and the level of uPAR, may be prognostic factors in gastric cancer.

摘要

目的

酪氨酸激酶受体家族的成员之一是 c-met 原癌基因的蛋白产物，它是肝细胞生长因子（HGF）的受体。HGF 是多种癌细胞有丝分裂和运动的有力刺激物，已发现它通过 HGF 受体模拟胃癌细胞的生长和进展。此外，尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）也在侵袭和转移中起重要作用。

材料和方法

使用免疫组织化学染色法检测 50 例石蜡包埋的胃癌组织中 c-met 蛋白的表达，并使用 ELISA 检测胃癌患者手术前后血清 uPAR 水平。

结果

在 50 例病例中，有 32 例（64%）表达 c-met 蛋白。c-met 蛋白表达与 TNM 分期显著相关（p<0.05），但其他预后因素不是显著变量。根据 Kaplan-Meier 图，未表达 c-met 蛋白的患者 1 年和 3 年总生存率分别为 94%和 70%，而表达 c-met 蛋白的患者分别为 81%和 33%，生存曲线显示出显著不同的预后（p=0.04）。在 26 例胃癌患者中，有 9 例（34.6%）观察到血清 uPAR 水平升高（>或=3257.8 pg/ml，对照+/-2SD），而在对照组中没有。手术前平均血清 uPAR 水平为 2980.8+/-616.2 pg/ml，手术后为 2404.7+/-455.9 pg/ml，手术后显著下降（p<0.05）。血清 uPAR 水平与淋巴结转移和血管侵犯显著相关（p<0.05）。