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基质金属蛋白酶-7(MMP-7)的过表达与肿瘤增殖相关,且与非小细胞肺癌的预后不良有关。

Overexpression of matrix metalloproteinase-7 (MMP-7) correlates with tumor proliferation, and a poor prognosis in non-small cell lung cancer.

作者信息

Liu Dage, Nakano Jun, Ishikawa Sinya, Yokomise Hiroyasu, Ueno Masaki, Kadota Kyuichi, Urushihara Masahide, Huang Cheng-Long

机构信息

Second Department of Surgery, Faculty of Medicine, Kagawa University, 1750-1 Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

出版信息

Lung Cancer. 2007 Dec;58(3):384-91. doi: 10.1016/j.lungcan.2007.07.005. Epub 2007 Aug 28.

DOI:10.1016/j.lungcan.2007.07.005
PMID:17728005
Abstract

BACKGROUND

Matrix metalloporteinase-7 (MMP-7) is a member of the MMP family, and it has been reported to play an important role in tumorigenesis, invasion and metastasis. We performed a retrospective study on the MMP-7 expression in non-small cell lung cancer (NSCLC) according to the clinical characteristics, biological markers and the Wnt1 expression.

PATIENTS AND METHODS

One hundred forty-seven postsurgical NSCLC patients were investigated. Immunohistochemistry was performed to evaluate the MMP-7 expression, the Ki-67 proliferation index, tumor angiogenesis and the Wnt1 expression. The TUNEL method was performed to investigate tumor apoptosis.

RESULTS

Seventy-six carcinomas (51.7%) were MMP-7-positive. The MMP-7 expression was significantly higher in squamous cell carcinomas than in adenocarcinomas (P<0.0001). The Ki-67 proliferation index was significantly higher in MMP-7-positvie tumors than in MMP-7-negative tumors (P=0.0003). However, there was no difference in the MMP-7 expression in relation to apoptosis or angiogenesis. Regarding its regulation, the MMP-7 expression significantly correlated with the Wnt1 expression (r=0.426, P<0.0001). The overall survival was significantly lower in patients with MMP-7-positive NSCLCs than in those with MMP-7-negative NSCLCs (P=0.0018). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 2.187; P=0.0023).

CONCLUSIONS

The overexpression of MMP-7 was associated with tumor proliferation, and a poor prognosis in NSCLCs. In addition, Wnt1 may play a critical role in regulating the intratumoral MMP-7 expression.

摘要

背景

基质金属蛋白酶-7(MMP-7)是MMP家族的成员,据报道其在肿瘤发生、侵袭和转移中起重要作用。我们根据临床特征、生物学标志物和Wnt1表达情况,对非小细胞肺癌(NSCLC)中MMP-7的表达进行了一项回顾性研究。

患者与方法

对147例NSCLC术后患者进行了调查。采用免疫组织化学法评估MMP-7表达、Ki-67增殖指数、肿瘤血管生成及Wnt1表达。采用TUNEL法研究肿瘤凋亡情况。

结果

76例癌组织(51.7%)MMP-7呈阳性。鳞状细胞癌中MMP-7表达显著高于腺癌(P<0.0001)。MMP-7阳性肿瘤的Ki-67增殖指数显著高于MMP-7阴性肿瘤(P=0.0003)。然而,MMP-7表达在凋亡或血管生成方面无差异。就其调控而言,MMP-7表达与Wnt1表达显著相关(r=0.426,P<0.0001)。MMP-7阳性NSCLC患者的总生存率显著低于MMP-7阴性NSCLC患者(P=0.0018)。Cox回归分析也表明MMP-7状态是一个显著的预后因素(风险比,2.187;P=0.0023)。

结论

MMP-7的过表达与NSCLC的肿瘤增殖及不良预后相关。此外,Wnt1可能在调节肿瘤内MMP-7表达中起关键作用。

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