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Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients
Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features,...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041800/ https://www.ncbi.nlm.nih.gov/pubmed/33846399 http://dx.doi.org/10.1038/s41598-021-86816-9 |
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author | Neuzillet, Cindy Marchais, Manon Vacher, Sophie Hilmi, Marc Schnitzler, Anne Meseure, Didier Leclere, Renaud Lecerf, Charlotte Dubot, Coraline Jeannot, Emmanuelle Klijanienko, Jerzy Mariani, Odette Calugaru, Valentin Hoffmann, Caroline Lesnik, Maria Badois, Nathalie Borcoman, Edith Piaggio, Eliane Kamal, Maud Le Tourneau, Christophe Bieche, Ivan |
author_facet | Neuzillet, Cindy Marchais, Manon Vacher, Sophie Hilmi, Marc Schnitzler, Anne Meseure, Didier Leclere, Renaud Lecerf, Charlotte Dubot, Coraline Jeannot, Emmanuelle Klijanienko, Jerzy Mariani, Odette Calugaru, Valentin Hoffmann, Caroline Lesnik, Maria Badois, Nathalie Borcoman, Edith Piaggio, Eliane Kamal, Maud Le Tourneau, Christophe Bieche, Ivan |
author_sort | Neuzillet, Cindy |
collection | PubMed |
description | Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis. |
format | Online Article Text |
id | pubmed-8041800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80418002021-04-13 Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients Neuzillet, Cindy Marchais, Manon Vacher, Sophie Hilmi, Marc Schnitzler, Anne Meseure, Didier Leclere, Renaud Lecerf, Charlotte Dubot, Coraline Jeannot, Emmanuelle Klijanienko, Jerzy Mariani, Odette Calugaru, Valentin Hoffmann, Caroline Lesnik, Maria Badois, Nathalie Borcoman, Edith Piaggio, Eliane Kamal, Maud Le Tourneau, Christophe Bieche, Ivan Sci Rep Article Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis. Nature Publishing Group UK 2021-04-12 /pmc/articles/PMC8041800/ /pubmed/33846399 http://dx.doi.org/10.1038/s41598-021-86816-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Neuzillet, Cindy Marchais, Manon Vacher, Sophie Hilmi, Marc Schnitzler, Anne Meseure, Didier Leclere, Renaud Lecerf, Charlotte Dubot, Coraline Jeannot, Emmanuelle Klijanienko, Jerzy Mariani, Odette Calugaru, Valentin Hoffmann, Caroline Lesnik, Maria Badois, Nathalie Borcoman, Edith Piaggio, Eliane Kamal, Maud Le Tourneau, Christophe Bieche, Ivan Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients |
title | Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients |
title_full | Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients |
title_fullStr | Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients |
title_full_unstemmed | Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients |
title_short | Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients |
title_sort | prognostic value of intratumoral fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041800/ https://www.ncbi.nlm.nih.gov/pubmed/33846399 http://dx.doi.org/10.1038/s41598-021-86816-9 |
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