Clinicopathological significance of matrix metalloproteinase-7 protein expression in esophageal cancer: a meta-analysis

Abstract

Background: The MMP-7 basement membrane and extracellular matrix may be essential for tumor invasion and metastasis, and the results presented herein showed a relationship between MMP-7 expression and esophageal cancer (EC). However, its clinicopathological value for EC patients remains inconsistent. To clarify their associations, a meta-analysis of the relevant published literature was conducted.

Materials and methods: Databases including PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, and Google Scholar were electronically searched. Only those studies analyzing MMP-7 expression in EC patients with regard to series of different demographic variables and clinicopathological stages (TNM stage, differentiation and invasion grade, and lymph-node [LN] metastasis) were eligible for inclusion. Summary odds ratios (ORs) were pooled in accordance with the random-effect model.

Results: Fourteen clinical cohort studies (tumor samples =935) were incorporated into the current meta-analysis. Results revealed that increased MMP-7 expression in EC patients was positively correlated to TNM stage III-IV (OR 3.04, 95% confidence interval [CI] 1.43-6.46; P=0.004). Similar connections were also detected in the differentiation grade, invasion grade, and LN metastasis (all P<0.05). Country-stratified analysis yielded significant association of elevated MMP-7 expression with EC in the People's Republic of China (PRC) under both TNM III-IV versus I-II and differentiation low versus high comparisons (TNM stage, OR 2.01, 95% CI 1.55-2.59, P<0.001; differentiation grade, OR 1.32, 95% CI 1.11-1.57, P=0.002). With regard to invasion grade and LN metastasis, significant association was observed in all the experimental subgroups (all P-values [PRC and Japan] were lower than 0.05).

Conclusion: These data showed an obvious connection between MMP-7 and TNM stages, differentiation grade, invasive grade, and LN metastasis of EC, indicating that overexpression of MMP-7 may be a suitable diagnostic biomarker for variation in EC clinicopathological features.

Keywords: MMP-7; esophagus carcinoma; statistical analysis.

Figure 1

Flowchart showing study-selection procedure. Note: Fourteen cohort studies were included in this meta-analysis.

Figure 2

Distribution of topic-related literature in electronic databases over the last decade.

Figure 3

Forest plots for the relationships between MMP-7 protein expression and the clinicopathological characteristics of esophageal cancer patients. Abbreviations: OR, odds ratio; CI, confidence interval; LN, lymph node.

Figure 4

Subgroup analyses of the relationships between MMP-7 protein expression and the clinicopathological characteristics of esophageal cancer patients. Abbreviations: OR, odds ratio; CI, confidence interval; SP, streptavidin–peroxidase; LN, lymph node.

Figure 4

Subgroup analyses of the relationships between MMP-7 protein expression and the clinicopathological characteristics of esophageal cancer patients. Abbreviations: OR, odds ratio; CI, confidence interval; SP, streptavidin–peroxidase; LN, lymph node.

Figure 5

Sensitivity analysis of the summary odds ratio coefficients on the associations between MMP-7 protein expression and the clinicopathological characteristics of esophageal cancer patients. Abbreviations: CI, confidence interval; LN, lymph node.

Figure 6

Funnel plot of publication biases on the associations between MMP-7 protein expression and the clinicopathological characteristics of esophageal cancer patients. Abbreviations: OR, odds ratio; SE, standard error; LN, lymph node.