Song Jian, Su Hong, Zhou Yang-Yang, Guo Liang-Liang
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Asian Pac J Cancer Prev. 2013;14(3):1615-21. doi: 10.7314/apjcp.2013.14.3.1615.
Matrix metalloproteinase 9 (MMP-9) is related to tumor invasion and metastasis. However, the role of MMP-9 expression in breast cancer survival remains controversial. The purpose of this study was to accomplish a more accurate estimation of the association between MMP-9 expression and survival results in breast cancer patients through meta-analysis.
A meta-analysis of published studies investigating the effects of positive MMP-9 expression on both relapse free survival (RFS) and overall survival (OS) was performed. Relevant literature was confirmed by searching electronic databases including PubMed, Ovid, EMBASE and China National Knowledge Infrastructure (CNKI) before November 1, 2012. Individual hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled HRs with 95% CIs were used to evaluate the strength of the association between positive MMP-9 expression and survival results of breast cancer patients. Funnel plot and Egger's regression tests were used to evaluate publication bias. Heterogeneity and sensitivity analysis was also conducted. All the work was completed using STATA.
A total of 2,344 patients from 15 evaluative studies were finally included. Pooled HRs and 95% CIs suggested that MMP-9 overexpression had an unfavorable impact on both OS (HR: 1.70, 95% CI: 1.41-2.04) and RFS (HR: 1.54, 95% CI: 1.17-2.01) in breast cancer patients. There was no significant heterogeneity observed in the studies reported for OS (P=0.360, I2=8.8%), but not RFS (P=0.002, I2=67%). Publication bias was absent among the studies both in OS and RFS cases (t=-0.54, P=0.605 and t=1.71, P=0.131, respectively). Omission of any single study had little effect on the combined risk estimates on sensitivity analysis.
The results of this meta-analysis suggest that positive MMP-9 expression confers a higher risk of relapse and a worse survival in patients with breast cancer. Larger prospective studies are now needed to evaluate the clinical utility of MMP-9 expression.
基质金属蛋白酶9（MMP - 9）与肿瘤侵袭和转移相关。然而，MMP - 9表达在乳腺癌生存中的作用仍存在争议。本研究的目的是通过荟萃分析更准确地评估MMP - 9表达与乳腺癌患者生存结果之间的关联。
对已发表的研究进行荟萃分析，这些研究调查了MMP - 9阳性表达对无复发生存期（RFS）和总生存期（OS）的影响。在2012年11月1日前，通过检索包括PubMed、Ovid、EMBASE和中国知网（CNKI）在内的电子数据库来确定相关文献。提取个体风险比（HRs）和95%置信区间（CIs），并使用合并的HRs及95% CIs来评估MMP - 9阳性表达与乳腺癌患者生存结果之间关联的强度。采用漏斗图和Egger回归检验来评估发表偏倚。还进行了异质性和敏感性分析。所有工作均使用STATA完成。
最终纳入了来自15项评估研究的2344例患者。合并的HRs和95% CIs表明，MMP - 9过表达对乳腺癌患者的OS（HR：1.70，95% CI：1.41 - 2.04）和RFS（HR：1.54，95% CI：1.17 - 2.01）均有不利影响。在报告的OS研究中未观察到显著异质性（P = 0.360，I² = 8.8%），但RFS研究中有显著异质性（P = 0.002，I² = 67%）。在OS和RFS研究中均不存在发表偏倚（分别为t = - 0.54，P = 0.605和t = 1.71，P = 0.131）。在敏感性分析中，遗漏任何一项研究对合并风险估计的影响都很小。
本荟萃分析结果表明，MMP - 9阳性表达使乳腺癌患者复发风险更高，生存更差。现在需要更大规模的前瞻性研究来评估MMP - 9表达的临床应用价值。
