MMP1-PAR1 轴与原发性胆囊癌临床结果的相关性。

Correlation between MMP1-PAR1 axis and clinical outcome of primary gallbladder carcinoma.

机构信息

Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.

出版信息

Jpn J Clin Oncol. 2011 Sep;41(9):1086-93. doi: 10.1093/jjco/hyr108. Epub 2011 Aug 10.

DOI:10.1093/jjco/hyr108

PMID:21835828

Abstract

OBJECTIVE

Matrix metalloprotease-1 and protease-activated receptor-1 axis plays an important role in many cancers, with activation often associated with poor survival. The aim of the present study was to determine whether the immunohistochemical detection of matrix metalloprotease-1 and protease-activated receptor-1 could provide useful information as novel therapeutic or prognostic factors in primary gallbladder carcinoma.

METHODS

Eighty-six gallbladder carcinoma tissues were evaluated by immunohistochemistry for matrix metalloprotease-1 and protease-activated receptor-1 expressions. The association of matrix metalloprotease-1 and protease-activated receptor-1 expressions with clinicopathological characteristics and the univariate survival analysis for the influence of matrix metalloprotease-1 and protease-activated receptor-1 expressions on the overall survival were analyzed.

RESULTS

Matrix metalloprotease-1 and protease-activated receptor-1 immunoreactivities were observed in 62 (72.1%) and 59 (68.6%) of the 86 gallbladder carcinoma cases, respectively. The tumors with the positive expressions of matrix metalloprotease-1 (P= 0.007) and protease-activated receptor-1 (P= 0.01) more frequently showed lymph node metastasis, respectively. In addition, the tumors with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 tended to show a deeper invasion depth (P= 0.006 and 0.008, respectively) and more frequent lymphovascular invasion (both P= 0.01). The Kaplan-Meier survival curves demonstrated that patients with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 had a significantly shorter survival time than those patients with their negative expression (both P= 0.02).

CONCLUSIONS

A subset of gallbladder carcinoma cases revealed the overexpression of matrix metalloprotease-1 and protease-activated receptor-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, matrix metalloprotease-1 and protease-activated receptor-1 expressions may be predictors for a poor prognosis in patients with gallbladder carcinoma. This is the first report describing about the involvement of matrix metalloprotease-1 and protease-activated receptor-1 axis in gallbladder carcinoma.

摘要

目的

基质金属蛋白酶-1 和蛋白酶激活受体-1 轴在许多癌症中发挥着重要作用，其激活通常与不良预后相关。本研究旨在确定基质金属蛋白酶-1 和蛋白酶激活受体-1 的免疫组织化学检测是否能为原发性胆囊癌的新型治疗或预后因素提供有用的信息。

方法

对 86 例胆囊癌组织进行基质金属蛋白酶-1 和蛋白酶激活受体-1 的免疫组织化学检测。分析基质金属蛋白酶-1 和蛋白酶激活受体-1 的表达与临床病理特征的关系，并对基质金属蛋白酶-1 和蛋白酶激活受体-1 的表达对总生存率的影响进行单因素生存分析。

结果

在 86 例胆囊癌病例中，有 62 例（72.1%）和 59 例（68.6%）的肿瘤观察到基质金属蛋白酶-1 和蛋白酶激活受体-1 的免疫反应活性。基质金属蛋白酶-1（P=0.007）和蛋白酶激活受体-1（P=0.01）阳性表达的肿瘤淋巴结转移更频繁。此外，基质金属蛋白酶-1 和蛋白酶激活受体-1 阳性表达的肿瘤更倾向于表现出更深的浸润深度（P=0.006 和 0.008）和更频繁的脉管侵犯（均 P=0.01）。Kaplan-Meier 生存曲线表明，基质金属蛋白酶-1 和蛋白酶激活受体-1 阳性表达的患者生存时间明显短于阴性表达的患者（均 P=0.02）。