High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1
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...
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doaj-07b2aa6f47c641bab69c28c9e2f50b012020-11-25T00:52:55ZengWileyCancer Medicine2045-76342019-11-018166995700510.1002/cam4.2576High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1Aaro Kasurinen0Silvia Gramolelli1Jaana Hagström2Alli Laitinen3Arto Kokkola4Yuichiro Miki5Kaisa Lehti6Masakazu Yashiro7Päivi M. Ojala8Camilla Böckelman9Caj Haglund10Translational Cancer Medicine Research Program Faculty of Medicine University of Helsinki Helsinki FinlandTranslational Cancer Medicine Research Program Faculty of Medicine University of Helsinki Helsinki FinlandDepartment of Pathology and Oral Pathology University of Helsinki and Helsinki University Hospital Helsinki FinlandTranslational Cancer Medicine Research Program Faculty of Medicine University of Helsinki Helsinki FinlandDepartment of Surgery University of Helsinki and Helsinki University Hospital Helsinki FinlandDepartment of Microbiology, Tumor and Cell Biology Karolinska Institute Stockholm SwedenDepartment of Microbiology, Tumor and Cell Biology Karolinska Institute Stockholm SwedenDepartment of Surgical Oncology Osaka City University Graduate School of Medicine Osaka JapanTranslational Cancer Medicine Research Program Faculty of Medicine University of Helsinki Helsinki FinlandTranslational Cancer Medicine Research Program Faculty of Medicine University of Helsinki Helsinki FinlandTranslational Cancer Medicine Research Program Faculty of Medicine University of Helsinki Helsinki FinlandAbstract 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.https://doi.org/10.1002/cam4.2576gastric cancermatrix metalloproteinase 14prognosisprospero homeobox protein 1survival |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aaro Kasurinen Silvia Gramolelli Jaana Hagström Alli Laitinen Arto Kokkola Yuichiro Miki Kaisa Lehti Masakazu Yashiro Päivi M. Ojala Camilla Böckelman Caj Haglund |
spellingShingle |
Aaro Kasurinen Silvia Gramolelli Jaana Hagström Alli Laitinen Arto Kokkola Yuichiro Miki Kaisa Lehti Masakazu Yashiro Päivi M. Ojala Camilla Böckelman Caj Haglund High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1 Cancer Medicine gastric cancer matrix metalloproteinase 14 prognosis prospero homeobox protein 1 survival |
author_facet |
Aaro Kasurinen Silvia Gramolelli Jaana Hagström Alli Laitinen Arto Kokkola Yuichiro Miki Kaisa Lehti Masakazu Yashiro Päivi M. Ojala Camilla Böckelman Caj Haglund |
author_sort |
Aaro Kasurinen |
title |
High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1 |
title_short |
High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1 |
title_full |
High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1 |
title_fullStr |
High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1 |
title_full_unstemmed |
High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1 |
title_sort |
high tissue mmp14 expression predicts worse survival in gastric cancer, particularly with a low prox1 |
publisher |
Wiley |
series |
Cancer Medicine |
issn |
2045-7634 |
publishDate |
2019-11-01 |
description |
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. |
topic |
gastric cancer matrix metalloproteinase 14 prognosis prospero homeobox protein 1 survival |
url |
https://doi.org/10.1002/cam4.2576 |
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