Send Orders for Reprints to reprints@benthamscience.ae Current Medicinal Chemistry, 2019, 26, 1-19 1 REVIEW ARTICLE 0929-8673/19 $58.00+.00 © 2019 Bentham Science Publishers Prognostic Impact of Tissue Inhibitor of Metalloproteinase-1 in Non- Small Cell Lung Cancer: Systematic Review and Meta-Analysis Gurudeeban Selvaraj a,c , Satyavani Kaliamurthi 1,a,c , Shuhuang Lin 2,b , Keren Gu 3,a,c and Dong-Qing Wei 4,a,d,* a Center of Interdisciplinary Sciences-Computational Life Sciences, College of Food Science and Engineer- ing, Henan University of Technology, Zhengzhou High-tech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China; b The Second School of Clinical Medicine, Guangdong Medical University, Dongguan, Guangdong 523808, China; c College of Chemistry, Chemical Engineering and Envi- ronment, Henan University of Technology, Zhengzhou High-tech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China; d The State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang, Shanghai, 200240, China A R T I C L E H I S T O R Y Received: November 02, 2017 Revised: April 06, 2018 Accepted: July 23, 2018 DOI: 10.2174/0929867325666180904114455 Abstract: Background and Objectives: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional natural matrixin inhibitor that is generally considered a negative regulator of cancer metastasis. Clinical studies reporting the prognostic value of TIMP-1 in non-small cell lung cancer (NSCLC) are inconsistent. Therefore, the present study aimed to determine the prognostic impact of TIMP-1 expression in NSCLC. Methods: Appropriate studies with full-text articles were identified in searches of the China National Knowledge Infrastructure (CNKI), Cochrane Library, PubMed, and Web of Science databases up to March 7, 2018. The pooled hazard ratio (HR) of overall survival with a 95% confidence interval (95% CI) was employed to assess the relationship between the expression of TIMP-1 and NSCLC patient survival. Results: The meta-analysis comprised 40 studies including 3,194 patients. Study outcomes indicated that high TIMP-1 expression is independently associated with poor overall survival (HR: 1.60; 95% CI: 1.50, 1.69; P < 0.00001) with 61% of heterogeneity. In addition, we ana- lyzed subgroups, including ethnicities, histological types, percentage of TIMP-1 expression levels, specimens, and tumor stage. All results were statistically significant. The outcome of our meta-analysis indicates that high expression levels of TIMP-1 are correlated with poor prognosis in patients with NSCLC. Conclusion: Expression levels of TIMP-1 represent a potential prognostic biomarker in NSCLC patients in addition to being a possible therapeutic target. Keywords: Antiapoptosis, cell proliferation, IHC, meta-analysis, non-small cell lung cancer, tumor invasion, tissue inhibitor of metalloproteinase-1. 1. INTRODUCTION Lung cancer is a malignancy with one of highest mortalities worldwide in both males and females, as *Address correspondence to this author at the State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnol- ogy, Shanghai Jiao Tong University, No: 800 Dongchuan Road, Minhang, Shanghai, 200240, China; Tel: 86-021-34204717; Fax: 86-021-34205709; E-mail: dqwei@sjtu.edu.cn reflected by an estimated 155,870 annual deaths, being higher than for any other type of cancer [1]. In contrast to the decline in lung cancer prevalence in the United States, United Kingdom and Canada, lung cancer prevalence continues to increase in China, potentially due to air pollution and genetic variants [2]. Lung can- cer can be categorized into two main histological types, small cell (SC) and the more widespread non-small cell