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MMP2 as an independent prognostic stratifier in oral cavity cancers

BACKGROUND: Around 25% of oral cavity squamous cell carcinoma (OCSCC) are not controlled by the standard of care, but there is currently no validated biomarker to identify those patients. Our objective was to determine a robust biomarker for severe OCSCC, using a biology-driven strategy. PATIENTS AN...

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Autores principales: Hoffmann, Caroline, Vacher, Sophie, Sirven, Philémon, Lecerf, Charlotte, Massenet, Lucile, Moreira, Aurélie, Surun, Aurore, Schnitzler, Anne, Klijanienko, Jerzy, Mariani, Odette, Jeannot, Emmanuelle, Badois, Nathalie, Lesnik, Maria, Choussy, Olivier, Le Tourneau, Christophe, Guillot-Delost, Maude, Kamal, Maud, Bieche, Ivan, Soumelis, Vassili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466851/
https://www.ncbi.nlm.nih.gov/pubmed/32934875
http://dx.doi.org/10.1080/2162402X.2020.1754094
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author Hoffmann, Caroline
Vacher, Sophie
Sirven, Philémon
Lecerf, Charlotte
Massenet, Lucile
Moreira, Aurélie
Surun, Aurore
Schnitzler, Anne
Klijanienko, Jerzy
Mariani, Odette
Jeannot, Emmanuelle
Badois, Nathalie
Lesnik, Maria
Choussy, Olivier
Le Tourneau, Christophe
Guillot-Delost, Maude
Kamal, Maud
Bieche, Ivan
Soumelis, Vassili
author_facet Hoffmann, Caroline
Vacher, Sophie
Sirven, Philémon
Lecerf, Charlotte
Massenet, Lucile
Moreira, Aurélie
Surun, Aurore
Schnitzler, Anne
Klijanienko, Jerzy
Mariani, Odette
Jeannot, Emmanuelle
Badois, Nathalie
Lesnik, Maria
Choussy, Olivier
Le Tourneau, Christophe
Guillot-Delost, Maude
Kamal, Maud
Bieche, Ivan
Soumelis, Vassili
author_sort Hoffmann, Caroline
collection PubMed
description BACKGROUND: Around 25% of oral cavity squamous cell carcinoma (OCSCC) are not controlled by the standard of care, but there is currently no validated biomarker to identify those patients. Our objective was to determine a robust biomarker for severe OCSCC, using a biology-driven strategy. PATIENTS AND METHODS: Tumor and juxtatumor secretome were analyzed in a prospective discovery cohort of 37 OCSCC treated by primary surgery. Independent biomarker validation was performed by RTqPCR in a retrospective cohort of 145 patients with similar clinical features. An 18-gene signature (18 G) predictive of the response to PD-1 blockade was evaluated in the same cohort. RESULTS: Among 29 deregulated molecules identified in a secretome analysis, including chemokines, cytokines, growth factors, and molecules related to tumor growth and tissue remodeling, only soluble MMP2 was a prognostic biomarker. In our validation cohort, high levels of MMP2 and CD276, and low levels of CXCL10 and STAT1 mRNA were associated with poor prognosis in univariate analysis (Kaplan-Meier). MMP2 (p = .001) and extra-nodal extension (ENE) (p = .006) were independent biomarkers of disease-specific survival (DSS) in multivariate analysis and defined prognostic groups with 5-year DSS ranging from 36% (MMP2highENE+) to 88% (MMP2lowENE-). The expression of 18 G was similar in the different prognostic groups, suggesting comparable responsiveness to anti-PD-1. CONCLUSION: High levels of MMP2 were an independent and validated prognostic biomarker, surpassing other molecules of a large panel of the tumor and immune-related processes, which may be used to select poor prognosis patients for intensified neoadjuvant or adjuvant regimens.
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spelling pubmed-74668512020-09-14 MMP2 as an independent prognostic stratifier in oral cavity cancers Hoffmann, Caroline Vacher, Sophie Sirven, Philémon Lecerf, Charlotte Massenet, Lucile Moreira, Aurélie Surun, Aurore Schnitzler, Anne Klijanienko, Jerzy Mariani, Odette Jeannot, Emmanuelle Badois, Nathalie Lesnik, Maria Choussy, Olivier Le Tourneau, Christophe Guillot-Delost, Maude Kamal, Maud Bieche, Ivan Soumelis, Vassili Oncoimmunology Original Research BACKGROUND: Around 25% of oral cavity squamous cell carcinoma (OCSCC) are not controlled by the standard of care, but there is currently no validated biomarker to identify those patients. Our objective was to determine a robust biomarker for severe OCSCC, using a biology-driven strategy. PATIENTS AND METHODS: Tumor and juxtatumor secretome were analyzed in a prospective discovery cohort of 37 OCSCC treated by primary surgery. Independent biomarker validation was performed by RTqPCR in a retrospective cohort of 145 patients with similar clinical features. An 18-gene signature (18 G) predictive of the response to PD-1 blockade was evaluated in the same cohort. RESULTS: Among 29 deregulated molecules identified in a secretome analysis, including chemokines, cytokines, growth factors, and molecules related to tumor growth and tissue remodeling, only soluble MMP2 was a prognostic biomarker. In our validation cohort, high levels of MMP2 and CD276, and low levels of CXCL10 and STAT1 mRNA were associated with poor prognosis in univariate analysis (Kaplan-Meier). MMP2 (p = .001) and extra-nodal extension (ENE) (p = .006) were independent biomarkers of disease-specific survival (DSS) in multivariate analysis and defined prognostic groups with 5-year DSS ranging from 36% (MMP2highENE+) to 88% (MMP2lowENE-). The expression of 18 G was similar in the different prognostic groups, suggesting comparable responsiveness to anti-PD-1. CONCLUSION: High levels of MMP2 were an independent and validated prognostic biomarker, surpassing other molecules of a large panel of the tumor and immune-related processes, which may be used to select poor prognosis patients for intensified neoadjuvant or adjuvant regimens. Taylor & Francis 2020-05-13 /pmc/articles/PMC7466851/ /pubmed/32934875 http://dx.doi.org/10.1080/2162402X.2020.1754094 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Hoffmann, Caroline
Vacher, Sophie
Sirven, Philémon
Lecerf, Charlotte
Massenet, Lucile
Moreira, Aurélie
Surun, Aurore
Schnitzler, Anne
Klijanienko, Jerzy
Mariani, Odette
Jeannot, Emmanuelle
Badois, Nathalie
Lesnik, Maria
Choussy, Olivier
Le Tourneau, Christophe
Guillot-Delost, Maude
Kamal, Maud
Bieche, Ivan
Soumelis, Vassili
MMP2 as an independent prognostic stratifier in oral cavity cancers
title MMP2 as an independent prognostic stratifier in oral cavity cancers
title_full MMP2 as an independent prognostic stratifier in oral cavity cancers
title_fullStr MMP2 as an independent prognostic stratifier in oral cavity cancers
title_full_unstemmed MMP2 as an independent prognostic stratifier in oral cavity cancers
title_short MMP2 as an independent prognostic stratifier in oral cavity cancers
title_sort mmp2 as an independent prognostic stratifier in oral cavity cancers
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466851/
https://www.ncbi.nlm.nih.gov/pubmed/32934875
http://dx.doi.org/10.1080/2162402X.2020.1754094
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