title: Predictive value of MMP-7 expression for response to chemotherapy and survival in patients with non-small cell lung cancer.
abstract: Fundamental studies have suggested that matrix metalloproteinases-7 (MMP-7) expression is associated with chemoresistance and constitutes a prognostic factor in several solid tumors. The present study assessed the prognostic and predictive value of MMP-7 in tumors of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. Immunohistochemistry was performed to evaluate the expression of MMP-7, apoptosis-related proteins Bcl-2, Bax, Fas and FasL and the Ki-67 proliferation marker. The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) method was performed to investigate tumor apoptosis. Ninety carcinomas (56.6%) were identified as high expression of MMP-7. Overexpression of MMP-7 was more frequent in adenocarcinomas than in squamous cell carcinomas (P = 0.032). The expression of MMP-7 was positively related with Ki-67 index and Bcl-2, but not apoptosis index. MMP-7 status was correlated inversely with response to chemotherapy in overall patients (response rates, 20.0% and 35.8%, for patients with high-MMP-7 and low-MMP-7 tumors, respectively, P = 0.036), especially in adenocarcinoma (P = 0.021), but not in patients with squamous cell carcinomas (P = 0.373). The overall survival was significantly lower in NSCLC patients with high MMP-7 than in those with low MMP-7 (P < 0.001). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 5.49 P = 0.001). These findings suggest that the expression level of MMP-7 in tumor cells is predictive of response to chemotherapy and outcome in patients with advanced NSCLC receiving platinum-based chemotherapy.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Tiantuo
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Benquan
authors.initials: B
authors.lastname: Wu
authors.forename: Xubing
authors.initials: X
authors.lastname: Huang
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Zhu
authors.forename: Jinghui
authors.initials: J
authors.lastname: Hou
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D020783:Matrix Metalloproteinase 7