Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma
Abstract Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-024-00511-x |
| _version_ | 1797209479426605056 |
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| author | Liuyang Cai Hengyan Zhu Qianqian Mou Po Yee Wong Linlin Lan Cherrie W. K. Ng Pu Lei Man Kit Cheung Daijuanru Wang Eddy W. Y. Wong Eric H. L. Lau Zenon W. C. Yeung Ronald Lai Katie Meehan Sherwood Fung Kwan Chee A. Chan Vivian W. Y. Lui Alfred S. L. Cheng Jun Yu Paul K. S. Chan Jason Y. K. Chan Zigui Chen |
| author_facet | Liuyang Cai Hengyan Zhu Qianqian Mou Po Yee Wong Linlin Lan Cherrie W. K. Ng Pu Lei Man Kit Cheung Daijuanru Wang Eddy W. Y. Wong Eric H. L. Lau Zenon W. C. Yeung Ronald Lai Katie Meehan Sherwood Fung Kwan Chee A. Chan Vivian W. Y. Lui Alfred S. L. Cheng Jun Yu Paul K. S. Chan Jason Y. K. Chan Zigui Chen |
| author_sort | Liuyang Cai |
| collection | DOAJ |
| description | Abstract Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer. |
| first_indexed | 2024-04-24T09:55:21Z |
| format | Article |
| id | doaj.art-6d1d6f4104b84fe4850c86de36df8238 |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-04-24T09:55:21Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-6d1d6f4104b84fe4850c86de36df82382024-04-14T11:09:12ZengNature Portfolionpj Biofilms and Microbiomes2055-50082024-04-0110111610.1038/s41522-024-00511-xIntegrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinomaLiuyang Cai0Hengyan Zhu1Qianqian Mou2Po Yee Wong3Linlin Lan4Cherrie W. K. Ng5Pu Lei6Man Kit Cheung7Daijuanru Wang8Eddy W. Y. Wong9Eric H. L. Lau10Zenon W. C. Yeung11Ronald Lai12Katie Meehan13Sherwood Fung14Kwan Chee A. Chan15Vivian W. Y. Lui16Alfred S. L. Cheng17Jun Yu18Paul K. S. Chan19Jason Y. K. Chan20Zigui Chen21Department of Microbiology, The Chinese University of Hong KongDepartment of Microbiology, The Chinese University of Hong KongDepartment of Microbiology, The Chinese University of Hong KongDepartment of Microbiology, The Chinese University of Hong KongDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong KongDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong KongDepartment of Microbiology, The Chinese University of Hong KongDepartment of Microbiology, The Chinese University of Hong KongDepartment of Microbiology, The Chinese University of Hong KongDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong KongDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong KongDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong KongDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong KongDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong KongDepartment of Chemical Pathology, The Chinese University of Hong KongDepartment of Chemical Pathology, The Chinese University of Hong KongGeorgia Cancer CenterSchool of Biomedical Sciences, The Chinese University of Hong KongDepartment of Medicine and Therapeutics, The Chinese University of Hong KongDepartment of Microbiology, The Chinese University of Hong KongDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong KongDepartment of Microbiology, The Chinese University of Hong KongAbstract Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.https://doi.org/10.1038/s41522-024-00511-x |
| spellingShingle | Liuyang Cai Hengyan Zhu Qianqian Mou Po Yee Wong Linlin Lan Cherrie W. K. Ng Pu Lei Man Kit Cheung Daijuanru Wang Eddy W. Y. Wong Eric H. L. Lau Zenon W. C. Yeung Ronald Lai Katie Meehan Sherwood Fung Kwan Chee A. Chan Vivian W. Y. Lui Alfred S. L. Cheng Jun Yu Paul K. S. Chan Jason Y. K. Chan Zigui Chen Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma npj Biofilms and Microbiomes |
| title | Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma |
| title_full | Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma |
| title_fullStr | Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma |
| title_full_unstemmed | Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma |
| title_short | Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma |
| title_sort | integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma |
| url | https://doi.org/10.1038/s41522-024-00511-x |
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