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Genetic Insights into Oral Cancer Microbiota: Ubiquitination Pathway Alterations and Fusobacterium Prevalence
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788245
*Corresponding author: (e-mail: amitdutt3@gmail.com).
Abstract
Background: The recent discovery of bacterial protein-based ubiquitination substrates has expanded understanding of pathogen recognition by tumor cells. Our recent study revealed elevated Fusobacterium nucleatum prevalence in tongue cancer, linked to distinctive inflammatory microenvironment. Here, we investigate whether genetic alterations in ubiquitination pathway genes influence the Fusobacterium status in oral cancer.
Materials and Methods: Analyzing 514 samples from the TCGA-HNSC cohort, we identified genetic alterations in ubiquitination pathway and correlated them with Fusobacterium abundance. Simultaneously, employing a co-culture model involving Fusobacterium nucleatum and oral cancer cells, we will conduct spatial-transcriptomics on 16 Fusobacterium-positive tongue cancer tissues with subsequent validation of findings in 1,500 patient samples.
Results: Our mutational analysis revealed higher occurrences of mutations in FBXW7, CUL9, and BIRC6 in Fusobacterium-high patients, while MYCBP2, RNF213, and CUL3 were significantly mutated in Fusobacterium-low patients. Expression analysis demonstrated lower CUL9 expression in Fusobacterium-high patients. Our functional validation underway involves a co-culture experimental model system at different time points and multiplicities of infection. To further explore Fusobacterium nucleatum's impact on the oral cancer microenvironment, spatial transcriptomics will be performed on tissues with varying Fusobacterium abundance. The results will be validated in a comprehensive cohort of 1,500 oral cancer samples and further investigated in orthotopic tongue cancer mouse models.
Conclusion: Overall, this study offers a comprehensive perspective on the influence of microbiota in the oral cancer microenvironment. The substantial sample size employed in this research positions it to yield valuable diagnostic and therapeutic insights, potentially leading to significant advancements in the management of patients with oral cancer.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (e-mail: amitdutt3@gmail.com).
Abstract
Background: The recent discovery of bacterial protein-based ubiquitination substrates has expanded understanding of pathogen recognition by tumor cells. Our recent study revealed elevated Fusobacterium nucleatum prevalence in tongue cancer, linked to distinctive inflammatory microenvironment. Here, we investigate whether genetic alterations in ubiquitination pathway genes influence the Fusobacterium status in oral cancer.
Materials and Methods: Analyzing 514 samples from the TCGA-HNSC cohort, we identified genetic alterations in ubiquitination pathway and correlated them with Fusobacterium abundance. Simultaneously, employing a co-culture model involving Fusobacterium nucleatum and oral cancer cells, we will conduct spatial-transcriptomics on 16 Fusobacterium-positive tongue cancer tissues with subsequent validation of findings in 1,500 patient samples.
Results: Our mutational analysis revealed higher occurrences of mutations in FBXW7, CUL9, and BIRC6 in Fusobacterium-high patients, while MYCBP2, RNF213, and CUL3 were significantly mutated in Fusobacterium-low patients. Expression analysis demonstrated lower CUL9 expression in Fusobacterium-high patients. Our functional validation underway involves a co-culture experimental model system at different time points and multiplicities of infection. To further explore Fusobacterium nucleatum's impact on the oral cancer microenvironment, spatial transcriptomics will be performed on tissues with varying Fusobacterium abundance. The results will be validated in a comprehensive cohort of 1,500 oral cancer samples and further investigated in orthotopic tongue cancer mouse models.
Conclusion: Overall, this study offers a comprehensive perspective on the influence of microbiota in the oral cancer microenvironment. The substantial sample size employed in this research positions it to yield valuable diagnostic and therapeutic insights, potentially leading to significant advancements in the management of patients with oral cancer.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India