Correlation Between MMP1-PAR1 Axis and Clinical Outcome of Primary Gallbladder Carcinoma
Correlation Between MMP1-PAR1 Axis and Clinical Outcome of Primary Gallbladder Carcinoma
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DOI：
10.1093/jjco/hyr108
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发表时间：
2011-09-01
影响因子：
2.4
通讯作者：
Li, Jinmao
中科院分区：
文献类型：
--
作者：
Du, Xilin;Wang, Shengzhi;Li, Jinmao
目的：基质金属蛋白酶-1和蛋白酶活化受体-1轴在多种癌症中起重要作用，其活化往往与较差的生存率相关。本研究的目的是确定基质金属蛋白酶-1和蛋白酶活化受体-1的免疫组化检测是否可以作为原发性胆囊癌的新的治疗或预后因素提供有用的信息。方法：应用免疫组化方法检测86例胆囊癌组织中基质金属蛋白酶-1及蛋白酶活化受体-1的表达。分析基质金属蛋白酶-1和蛋白酶活化受体-1表达与临床病理特征的关系，并分析基质金属蛋白酶-1和蛋白酶活化受体-1表达对总生存率影响的单因素生存分析。结果：86例胆囊癌患者中有62例（72.1%）出现基质金属蛋白酶-1免疫反应，59例（68.6%）出现蛋白酶活化受体-1免疫反应。基质金属蛋白酶-1 （P = 0.007）和蛋白酶活化受体-1 （P = 0.01）阳性表达的肿瘤更容易出现淋巴结转移。此外，基质金属蛋白酶-1和蛋白酶活化受体-1阳性表达的肿瘤，其浸润深度较深（P = 0.006和0.008），淋巴血管浸润频率较高（P = 0.01）。Kaplan-Meier生存曲线显示基质金属蛋白酶-1和蛋白酶活化受体-1阳性表达患者的生存时间明显短于阴性表达患者（P = 0.02）。结论：部分胆囊癌患者表现出基质金属蛋白酶-1和蛋白酶活化受体-1的过表达，并伴有进行性的病理特征和侵袭性的临床病程。因此，基质金属蛋白酶-1和蛋白酶活化受体-1的表达可能是胆囊癌患者预后不良的预测因子。本文首次报道了基质金属蛋白酶-1和蛋白酶活化受体-1轴在胆囊癌中的作用。
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.