Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer

Abstract Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) accounts for the highest cancer morbidity and mortality among men in India. It has been observed that about one-third of individuals with oral leukoplakia, a dysplastic precancerous lesion in the oral cavity, progress to or...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Debodipta Das, Arindam Maitra, Chinmay K. Panda, Sandip Ghose, Bidyut Roy, Rajiv Sarin, Partha P. Majumder
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/6debb581d1164ff6b5e4e6f54c7c0b6e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6debb581d1164ff6b5e4e6f54c7c0b6e
record_format	dspace
spelling	oai:doaj.org-article:6debb581d1164ff6b5e4e6f54c7c0b6e2021-12-02T16:50:32ZGenes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer10.1038/s41525-021-00195-82056-7944https://doaj.org/article/6debb581d1164ff6b5e4e6f54c7c0b6e2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00195-8https://doaj.org/toc/2056-7944Abstract Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) accounts for the highest cancer morbidity and mortality among men in India. It has been observed that about one-third of individuals with oral leukoplakia, a dysplastic precancerous lesion in the oral cavity, progress to oral cancer. We aimed to identify systematic transcriptomic changes as a normal tissue in the oral cavity progresses to frank OSCC-GB. Seventy-two OSCC-GB patients, from multiple hospitals, were recruited, and transcriptome analysis of tumor and adjacent normal tissue (of all patients) and adjacent leukoplakia tissue (of a subset of 25 unselected patients with concomitant leukoplakia) was performed. We have identified many differences in the transcriptomic profiles between OSCC-GB and squamous cell carcinoma of the head and neck regions. Compared to the normal/precancerous tissue, significant enrichment of ECM−receptor interaction, PI3K-Akt signaling, cytokine−cytokine receptor interaction, focal adhesion, and cell cycle pathways were observed in OSCC-GB. Using gene set enrichment analysis, we identified a profound role of interferon receptor signaling in tumor growth by activating immune evasion mechanisms. The role of tumor-infiltrating immune cells further supported the growth and immunosuppressive mechanism of tumor tissues. Some immune evasion genes—CD274, CD80, and IDO1—were found to be activated even in the precancerous tissue. Taken together, our findings provide a clear insight into the sequential genetic dysregulation associated with progression to oral cancer. This insight provides a window to the development of predictive biomarkers and therapeutic targets for gingivo-buccal oral cancer.Debodipta DasArindam MaitraChinmay K. PandaSandip GhoseBidyut RoyRajiv SarinPartha P. MajumderNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Debodipta Das Arindam Maitra Chinmay K. Panda Sandip Ghose Bidyut Roy Rajiv Sarin Partha P. Majumder Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer
description	Abstract Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) accounts for the highest cancer morbidity and mortality among men in India. It has been observed that about one-third of individuals with oral leukoplakia, a dysplastic precancerous lesion in the oral cavity, progress to oral cancer. We aimed to identify systematic transcriptomic changes as a normal tissue in the oral cavity progresses to frank OSCC-GB. Seventy-two OSCC-GB patients, from multiple hospitals, were recruited, and transcriptome analysis of tumor and adjacent normal tissue (of all patients) and adjacent leukoplakia tissue (of a subset of 25 unselected patients with concomitant leukoplakia) was performed. We have identified many differences in the transcriptomic profiles between OSCC-GB and squamous cell carcinoma of the head and neck regions. Compared to the normal/precancerous tissue, significant enrichment of ECM−receptor interaction, PI3K-Akt signaling, cytokine−cytokine receptor interaction, focal adhesion, and cell cycle pathways were observed in OSCC-GB. Using gene set enrichment analysis, we identified a profound role of interferon receptor signaling in tumor growth by activating immune evasion mechanisms. The role of tumor-infiltrating immune cells further supported the growth and immunosuppressive mechanism of tumor tissues. Some immune evasion genes—CD274, CD80, and IDO1—were found to be activated even in the precancerous tissue. Taken together, our findings provide a clear insight into the sequential genetic dysregulation associated with progression to oral cancer. This insight provides a window to the development of predictive biomarkers and therapeutic targets for gingivo-buccal oral cancer.
format	article
author	Debodipta Das Arindam Maitra Chinmay K. Panda Sandip Ghose Bidyut Roy Rajiv Sarin Partha P. Majumder
author_facet	Debodipta Das Arindam Maitra Chinmay K. Panda Sandip Ghose Bidyut Roy Rajiv Sarin Partha P. Majumder
author_sort	Debodipta Das
title	Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer
title_short	Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer
title_full	Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer
title_fullStr	Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer
title_full_unstemmed	Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer
title_sort	genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6debb581d1164ff6b5e4e6f54c7c0b6e
work_keys_str_mv	AT debodiptadas genesandpathwaysmonotonicallydysregulatedduringprogressionfromnormalthroughleukoplakiatogingivobuccaloralcancer AT arindammaitra genesandpathwaysmonotonicallydysregulatedduringprogressionfromnormalthroughleukoplakiatogingivobuccaloralcancer AT chinmaykpanda genesandpathwaysmonotonicallydysregulatedduringprogressionfromnormalthroughleukoplakiatogingivobuccaloralcancer AT sandipghose genesandpathwaysmonotonicallydysregulatedduringprogressionfromnormalthroughleukoplakiatogingivobuccaloralcancer AT bidyutroy genesandpathwaysmonotonicallydysregulatedduringprogressionfromnormalthroughleukoplakiatogingivobuccaloralcancer AT rajivsarin genesandpathwaysmonotonicallydysregulatedduringprogressionfromnormalthroughleukoplakiatogingivobuccaloralcancer AT parthapmajumder genesandpathwaysmonotonicallydysregulatedduringprogressionfromnormalthroughleukoplakiatogingivobuccaloralcancer
_version_	1718383044351492096

Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer

Ejemplares similares