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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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