Prognostic Value of Tissue Inhibitor of Metalloproteinase-2 Expression in Patients with Non–Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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 (<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. CONCLUSIONS: 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.