High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1

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Kasurinen , A , Gramolelli , S , Hagström , J , Laitinen , A , Kokkola , A , Miki , Y , Lehti , K , Yashiro , M , Ojala , P M , Böckelman , C & Haglund , C 2019 , ' High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1 ' , Cancer medicine , vol. 8 , no. 16 , pp. 6995-7005 . https://doi.org/10.1002/cam4.2576

Title: High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1
Author: Kasurinen, Aaro; Gramolelli, Silvia; Hagström, Jaana; Laitinen, Alli; Kokkola, Arto; Miki, Yuichiro; Lehti, Kaisa; Yashiro, Masakazu; Ojala, Päivi M.; Böckelman, Camilla; Haglund, Caj
Contributor: University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, HUS Head and Neck Center
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, HUS Abdominal Center
University of Helsinki, INDIVIDRUG - Individualized Drug Therapy
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, Clinicum
University of Helsinki, HUS Abdominal Center
Date: 2019-11
Language: eng
Number of pages: 11
Belongs to series: Cancer medicine
ISSN: 2045-7634
URI: http://hdl.handle.net/10138/307761
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.
Subject: 3122 Cancers
gastric cancer
matrix metalloproteinase 14
prognosis
prospero homeobox protein 1
survival
TUMOR INVASION
PROGNOSIS
CELL-LINES
ESTABLISHMENT
MMP-9
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