Abstract
Matrix metalloproteinase 14 (MMP14), a membrane‐associated matrix metalloproteinase, has been shown to influence the invasion and metastasis of several solid tumors. Prospero homeobox protein 1 (PROX1), involved in the development and cell fate determination, is also expressed in malignant diseases functioning either as a tumor‐suppressing or oncogenic factor. In certain cancers PROX1 appears to transcriptionally suppress MMP14 expression. This study, therefore, aimed to explore the association between MMP14 and PROX1 and understand their potential as prognostic biomarkers in gastric cancer. The cohort consisted of 313 individuals operated for gastric adenocarcinoma between 2000 and 2009 in the Department of Surgery, Helsinki University Hospital. MMP14 and PROX1 expressions were studied using immunohistochemistry in the patient sample and using immunoblotting and immunofluorescence in gastric cancer cell lines. We generated survival curves using the Kaplan‐Meier method, determining significance via the log‐rank test. A high MMP14 expression associated with being ≥67 years (P = .041), while a positive nuclear PROX1 expression associated with tumors of a diffuse histological type (P = .041) and a high cytoplasmic PROX1 expression (P < .001). Five‐year disease‐specific survival among patients with a high MMP14 expression was 35.9% (95% confidence interval [CI] 24.9‐46.9), compared to 45.3% (95% CI 38.0‐52.6) for patients with a low MMP14 (P = .030). Survival was worse specifically among those with a high MMP14 and absent nuclear PROX1 expression (hazard ratio [HR] 1.65; 95% CI 1.09‐2.51; P = .019). Thus, this study confirms that a high MMP14 expression predicts a worse survival in gastric cancer, revealing for the first time that survival is particularly worse when PROX1 is low.
Highlights
Gastric cancer is one of the most common malignancies worldwide, featuring a poor prognosis largely due to its late diagnosis
PROX1 was recently shown to suppress Matrix metalloproteinase 14 (MMP14) expression in breast cancer, as well as hepatocellular and colorectal carcinoma; here we showed that survival is worse among those gastric cancer patients with a high MMP14 and a low PROX1 expression.[21]
We confirm that survival is worse among gastric cancer patients with a high MMP14 tissue expression and, for the first time, show that survival is worse when PROX1 is low
Summary
The funders played no role in the study design, data collection or analysis, the decision to publish, or in the preparation of the manuscript
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