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Prognostic value of tissue inhibitor of metalloproteinase-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis

Tissue inhibitor of metalloproteinase-2 (TIMP-2) is a small secretory glycoprotein with anti-matrix metalloproteinase activity. Data on the value of TIMP-2 as a prognostic factor in non-small cell lung cancer (NSCLC) are discordant and remain controversial. A systematic review and meta-analysis was...

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Published in:PloS one 2015-04, Vol.10 (4), p.e0124230-e0124230
Main Authors: Zhu, Lin, Yu, Hong, Liu, Shi-Yuan, Xiao, Xiang-Sheng, Dong, Wei-Hua, Chen, Yi-Nan, Xu, Wei, Zhu, Tong
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Zhu, Tong
description Tissue inhibitor of metalloproteinase-2 (TIMP-2) is a small secretory glycoprotein with anti-matrix metalloproteinase activity. Data on the value of TIMP-2 as a prognostic factor in non-small cell lung cancer (NSCLC) are discordant and remain controversial. A systematic review and meta-analysis was performed to explore this issue. We identified the relevant literature by searching the PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang Data databases (search terms: "non-small cell lung cancer" or "NSCLC" or "Lung Carcinoma, Non-Small-Cell", "Tissue Inhibitor of Metalloproteinase-2" or "TIMP-2", and "prognosis" or "prognostic" or "survive") for updates prior to March 1, 2014. The pooled hazard ratio (HR) of overall survival with a 95% confidence interval (95% CI) was used to evaluate the strength of the association between positive TIMP-2 expression and survival in patients with NSCLC. We included 12 studies in our systematic review; five studies involving 399 patients with NSCLC were meta-analyzed. The pooled HR of all included patients was 0.57 (95% CI: 0.43-0.77), and the HRs of subgroup analysis according to stage (I-IV), testing method (immunohistochemistry) and high TIMP-2 expression percentage (
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Data on the value of TIMP-2 as a prognostic factor in non-small cell lung cancer (NSCLC) are discordant and remain controversial. A systematic review and meta-analysis was performed to explore this issue. We identified the relevant literature by searching the PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang Data databases (search terms: "non-small cell lung cancer" or "NSCLC" or "Lung Carcinoma, Non-Small-Cell", "Tissue Inhibitor of Metalloproteinase-2" or "TIMP-2", and "prognosis" or "prognostic" or "survive") for updates prior to March 1, 2014. The pooled hazard ratio (HR) of overall survival with a 95% confidence interval (95% CI) was used to evaluate the strength of the association between positive TIMP-2 expression and survival in patients with NSCLC. We included 12 studies in our systematic review; five studies involving 399 patients with NSCLC were meta-analyzed. 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Performed the experiments: HY LZ TZ YNC. Analyzed the data: LZ SYL WHD WX. Contributed reagents/materials/analysis tools: TZ YNC WHD WX XSX. Wrote the paper: LZ HY YNC TZ.</notes><notes>Competing Interests: The authors have the following interests: co-author Tong Zhu is employed by Shanghai United Imaging Healthcare Co., Ltd. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.</notes><abstract>Tissue inhibitor of metalloproteinase-2 (TIMP-2) is a small secretory glycoprotein with anti-matrix metalloproteinase activity. Data on the value of TIMP-2 as a prognostic factor in non-small cell lung cancer (NSCLC) are discordant and remain controversial. A systematic review and meta-analysis was performed to explore this issue. We identified the relevant literature by searching the PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang Data databases (search terms: "non-small cell lung cancer" or "NSCLC" or "Lung Carcinoma, Non-Small-Cell", "Tissue Inhibitor of Metalloproteinase-2" or "TIMP-2", and "prognosis" or "prognostic" or "survive") for updates prior to March 1, 2014. The pooled hazard ratio (HR) of overall survival with a 95% confidence interval (95% CI) was used to evaluate the strength of the association between positive TIMP-2 expression and survival in patients with NSCLC. We included 12 studies in our systematic review; five studies involving 399 patients with NSCLC were meta-analyzed. The pooled HR of all included patients was 0.57 (95% CI: 0.43-0.77), and the HRs of subgroup analysis according to stage (I-IV), testing method (immunohistochemistry) and high TIMP-2 expression percentage (&lt;50%) were 0.63 (95% CI: 0.43-0.92), 0.55 (95% CI: 0.41-0.74), and 0.50 (95% CI: 0.28-0.88), respectively. These data suggested that high TIMP-2 expression is associated with favorable prognosis in NSCLC. The meta-analysis did not reveal heterogeneity or publication bias. TIMP-2 expression indicates favorable prognosis in patients with NSCLC; as a protective factor, it could help predict outcome and may guide clinical therapy in the future.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25905787</pmid><doi>10.1371/journal.pone.0124230</doi><oa>free_for_read</oa></addata></record>
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subjects Analysis
Biomarkers, Tumor - metabolism
Cancer
Cancer therapies
Carcinoma, Non-Small-Cell Lung - enzymology
Care and treatment
Confidence intervals
Female
Glycoproteins
Heterogeneity
Hospitals
Humans
Immunohistochemistry
Inhibitors
Lung cancer
Lung carcinoma
Lung diseases
Lung Neoplasms - enzymology
Male
Matrix metalloproteinase
Medical ethics
Medical imaging
Medical prognosis
Medical research
Meta-analysis
Metalloproteinase
Metastasis
Middle Aged
Mutation
Non-small cell lung cancer
Non-small cell lung carcinoma
Patients
Prognosis
Proteins
Small cell lung cancer
Small cell lung carcinoma
Subgroups
Survival
Systematic review
Test procedures
Tissue inhibitor of metalloproteinase 2
Tissue Inhibitor of Metalloproteinase-2 - metabolism
Tissues
title Prognostic value of tissue inhibitor of metalloproteinase-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis
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