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Overexpression of MMP14 predicts the poor prognosis in gastric cancer: Meta-analysis and database validation
Xikai Wang1, Qinghe Meng2, Yuanyuan Wang3
1School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Background:
Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.
Methods:
We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.
Results:
High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32-2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15-1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.
Conclusion:
High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.
Insights
High matrix metalloproteinase 14 (MMP14) expression correlates with a worse prognosis in gastric cancer (GC). MMP14 may serve as a prognostic factor and therapeutic target for GC patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinase 14 (MMP14) expression is implicated in gastric cancer (GC) prognosis, but existing research presents conflicting findings.
- Clarifying the prognostic role of MMP14 is crucial for understanding GC progression and patient outcomes.
Purpose of the Study:
- To evaluate the association between MMP14 expression and prognostic outcomes in gastric cancer (GC).
- To determine if MMP14 can serve as a prognostic biomarker and potential therapeutic target for GC.
Main Methods:
- Systematic literature search of PubMed, Web of Science, Embase, and Cochrane Library for studies on MMP14 and GC prognosis.
- Meta-analysis of hazard ratios (HR) and confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS).
- Validation using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, alongside bioinformatics analysis.
Main Results:
- High MMP14 expression is significantly associated with shorter OS and RFS in GC patients (HR > 1, P < .01).
- Elevated MMP14 levels correlate with adverse prognostic factors including poor differentiation, deeper invasion, lymph node metastasis, distant metastasis, and advanced stage.
- TCGA and GEO data confirm MMP14 overexpression in GC tissues and its association with poorer survival outcomes.
Conclusions:
- High MMP14 expression is a significant indicator of poor prognosis in gastric cancer.
- MMP14 represents a potential prognostic biomarker and a promising therapeutic target for gastric cancer.
