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Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers
Purpose/Objective(s): Microbiome has been shown to affect tumorigenesis by promoting inflammation. However, the association between the upper aerodigestive microbiome and head and neck squamous cell carcinoma (HNSCC) is not well established. Hypoxia is a modifiable factor associated with poor radiat...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778747/ https://www.ncbi.nlm.nih.gov/pubmed/36555172 http://dx.doi.org/10.3390/ijms232415531 |
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author | Dhakal, Aastha Upadhyay, Rituraj Wheeler, Caroline Hoyd, Rebecca Karivedu, Vidhya Gamez, Mauricio E. Valentin, Sasha Vanputten, Meade Bhateja, Priyanka Bonomi, Marcelo Konieczkowski, David J. Baliga, Sujith Mitchell, Darrion L. Grecula, John C. Blakaj, Dukagjin M. Denko, Nicholas C. Jhawar, Sachin R. Spakowicz, Daniel |
author_facet | Dhakal, Aastha Upadhyay, Rituraj Wheeler, Caroline Hoyd, Rebecca Karivedu, Vidhya Gamez, Mauricio E. Valentin, Sasha Vanputten, Meade Bhateja, Priyanka Bonomi, Marcelo Konieczkowski, David J. Baliga, Sujith Mitchell, Darrion L. Grecula, John C. Blakaj, Dukagjin M. Denko, Nicholas C. Jhawar, Sachin R. Spakowicz, Daniel |
author_sort | Dhakal, Aastha |
collection | PubMed |
description | Purpose/Objective(s): Microbiome has been shown to affect tumorigenesis by promoting inflammation. However, the association between the upper aerodigestive microbiome and head and neck squamous cell carcinoma (HNSCC) is not well established. Hypoxia is a modifiable factor associated with poor radiation response. Our study analyzed the HNSCC tumor samples from The Cancer Genome Atlas (TCGA) to investigate the relationship between different HNSCC tumor subsites, hypoxia, and local tumor microbiome composition. Results: A total of 357 patients were included [Oral cavity (OC) = 226, Oropharynx (OPx) = 53, and Larynx/Hypopharynx (LHPx) = 78], of which 12.8%, 71.7%, and 10.3%, respectively, were HPV positive. The mean (SD) hypoxia scores were 30.18 (11.10), 24.31 (14.13), and 29.53 (12.61) in OC, OPx, and LHPx tumors, respectively, with higher values indicating greater hypoxia. The hypoxia score was significantly higher for OC tumors compared to OPx (p = 0.044) and LHPx (p = 0.002). There was no significant correlation between hypoxia and HPV status. Pseudomonas sp. in OC, Actinomyces sp. and Sulfurimonas sp. in OPx, and Filifactor, Pseudomonas and Actinomyces sp. in LHPx had the strongest association with the hypoxia score. Materials/Methods: Tumor RNAseq samples from TCGA were processed, and the R package “tmesig” was used to calculate gene expression signature, including the Buffa hypoxia (BH) score, a validated hypoxia signature using 52 hypoxia-regulated genes. Microbe relative abundances were modeled with primary tumor location and a high vs. low tertile BH score applying a gamma-distributed generalized linear regression using the “stats” package in R, with adjusted p-value < 0.05 considered significant. Conclusions: In our study, oral cavity tumors were found to be more hypoxic compared to other head and neck subsites, which could potentially contribute to their radiation resistance. For each subsite, distinct microbial populations were over-represented in hypoxic tumors in a subsite-specific manner. Further studies focusing on an association between microbiome, hypoxia, and patient outcomes are warranted. |
format | Online Article Text |
id | pubmed-9778747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97787472022-12-23 Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers Dhakal, Aastha Upadhyay, Rituraj Wheeler, Caroline Hoyd, Rebecca Karivedu, Vidhya Gamez, Mauricio E. Valentin, Sasha Vanputten, Meade Bhateja, Priyanka Bonomi, Marcelo Konieczkowski, David J. Baliga, Sujith Mitchell, Darrion L. Grecula, John C. Blakaj, Dukagjin M. Denko, Nicholas C. Jhawar, Sachin R. Spakowicz, Daniel Int J Mol Sci Brief Report Purpose/Objective(s): Microbiome has been shown to affect tumorigenesis by promoting inflammation. However, the association between the upper aerodigestive microbiome and head and neck squamous cell carcinoma (HNSCC) is not well established. Hypoxia is a modifiable factor associated with poor radiation response. Our study analyzed the HNSCC tumor samples from The Cancer Genome Atlas (TCGA) to investigate the relationship between different HNSCC tumor subsites, hypoxia, and local tumor microbiome composition. Results: A total of 357 patients were included [Oral cavity (OC) = 226, Oropharynx (OPx) = 53, and Larynx/Hypopharynx (LHPx) = 78], of which 12.8%, 71.7%, and 10.3%, respectively, were HPV positive. The mean (SD) hypoxia scores were 30.18 (11.10), 24.31 (14.13), and 29.53 (12.61) in OC, OPx, and LHPx tumors, respectively, with higher values indicating greater hypoxia. The hypoxia score was significantly higher for OC tumors compared to OPx (p = 0.044) and LHPx (p = 0.002). There was no significant correlation between hypoxia and HPV status. Pseudomonas sp. in OC, Actinomyces sp. and Sulfurimonas sp. in OPx, and Filifactor, Pseudomonas and Actinomyces sp. in LHPx had the strongest association with the hypoxia score. Materials/Methods: Tumor RNAseq samples from TCGA were processed, and the R package “tmesig” was used to calculate gene expression signature, including the Buffa hypoxia (BH) score, a validated hypoxia signature using 52 hypoxia-regulated genes. Microbe relative abundances were modeled with primary tumor location and a high vs. low tertile BH score applying a gamma-distributed generalized linear regression using the “stats” package in R, with adjusted p-value < 0.05 considered significant. Conclusions: In our study, oral cavity tumors were found to be more hypoxic compared to other head and neck subsites, which could potentially contribute to their radiation resistance. For each subsite, distinct microbial populations were over-represented in hypoxic tumors in a subsite-specific manner. Further studies focusing on an association between microbiome, hypoxia, and patient outcomes are warranted. MDPI 2022-12-08 /pmc/articles/PMC9778747/ /pubmed/36555172 http://dx.doi.org/10.3390/ijms232415531 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Dhakal, Aastha Upadhyay, Rituraj Wheeler, Caroline Hoyd, Rebecca Karivedu, Vidhya Gamez, Mauricio E. Valentin, Sasha Vanputten, Meade Bhateja, Priyanka Bonomi, Marcelo Konieczkowski, David J. Baliga, Sujith Mitchell, Darrion L. Grecula, John C. Blakaj, Dukagjin M. Denko, Nicholas C. Jhawar, Sachin R. Spakowicz, Daniel Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers |
title | Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers |
title_full | Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers |
title_fullStr | Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers |
title_full_unstemmed | Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers |
title_short | Association between Tumor Microbiome and Hypoxia across Anatomic Subsites of Head and Neck Cancers |
title_sort | association between tumor microbiome and hypoxia across anatomic subsites of head and neck cancers |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778747/ https://www.ncbi.nlm.nih.gov/pubmed/36555172 http://dx.doi.org/10.3390/ijms232415531 |
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