Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach

Background: The mechanisms of carcinogenesis from viral infections are extraordinarily complex and not well understood. Traditional methods of analyzing RNA-sequencing data may not be sufficient for unraveling complicated interactions between viruses and host cells. Using RNA and DNA-sequencing data...

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Autores principales:	Lindsay M. Wong, Wei Tse Li, Neil Shende, Joseph C. Tsai, Jiayan Ma, Jaideep Chakladar, Aditi Gnanasekar, Yuanhao Qu, Kypros Dereschuk, Jessica Wang-Rodriguez, Weg M. Ongkeko
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Head and neck squamous cell carcinoma Cervical squamous cell carcinoma and endocervical adenocarcinoma Liver hepatocellular carcinoma Stomach adenocarcinoma Human papillomavirus Hepatitis B Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/42db16df2cf14ea897710911650e674c
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spelling	oai:doaj.org-article:42db16df2cf14ea897710911650e674c2021-11-28T04:30:00ZAnalysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach2001-037010.1016/j.csbj.2021.11.013https://doaj.org/article/42db16df2cf14ea897710911650e674c2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2001037021004785https://doaj.org/toc/2001-0370Background: The mechanisms of carcinogenesis from viral infections are extraordinarily complex and not well understood. Traditional methods of analyzing RNA-sequencing data may not be sufficient for unraveling complicated interactions between viruses and host cells. Using RNA and DNA-sequencing data from The Cancer Genome Atlas (TCGA), we aim to explore whether virus-induced tumors exhibit similar immune-associated (IA) dysregulations using a new algorithm we developed that focuses on the most important biological mechanisms involved in virus-induced cancers. Differential expression, survival correlation, and clinical variable correlations were used to identify the most clinically relevant IA genes dysregulated in 5 virus-induced cancers (HPV-induced head and neck squamous cell carcinoma, HPV-induced cervical cancer, EBV-induced stomach cancer, HBV-induced liver cancer, and HCV-induced liver cancer) after which a mechanistic approach was adopted to identify pathways implicated in IA gene dysregulation. Results: Our results revealed that IA dysregulations vary with the cancer type and the virus type, but cytokine signaling pathways are dysregulated in all virus-induced cancers. Furthermore, we also found that important similarities exist between all 5 virus-induced cancers in dysregulated clinically relevant oncogenic signatures and IA pathways. Finally, we also discovered potential mechanisms for genomic alterations to induce IA gene dysregulations using our algorithm. Conclusions: Our study offers a new approach to mechanism identification through integrating functional annotations and large-scale sequencing data, which may be invaluable to the discovery of new immunotherapy targets for virus-induced cancers.Lindsay M. WongWei Tse LiNeil ShendeJoseph C. TsaiJiayan MaJaideep ChakladarAditi GnanasekarYuanhao QuKypros DereschukJessica Wang-RodriguezWeg M. OngkekoElsevierarticleHead and neck squamous cell carcinomaCervical squamous cell carcinoma and endocervical adenocarcinomaLiver hepatocellular carcinomaStomach adenocarcinomaHuman papillomavirusHepatitis BBiotechnologyTP248.13-248.65ENComputational and Structural Biotechnology Journal, Vol 19, Iss , Pp 6240-6254 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Head and neck squamous cell carcinoma Cervical squamous cell carcinoma and endocervical adenocarcinoma Liver hepatocellular carcinoma Stomach adenocarcinoma Human papillomavirus Hepatitis B Biotechnology TP248.13-248.65
spellingShingle	Head and neck squamous cell carcinoma Cervical squamous cell carcinoma and endocervical adenocarcinoma Liver hepatocellular carcinoma Stomach adenocarcinoma Human papillomavirus Hepatitis B Biotechnology TP248.13-248.65 Lindsay M. Wong Wei Tse Li Neil Shende Joseph C. Tsai Jiayan Ma Jaideep Chakladar Aditi Gnanasekar Yuanhao Qu Kypros Dereschuk Jessica Wang-Rodriguez Weg M. Ongkeko Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach
description	Background: The mechanisms of carcinogenesis from viral infections are extraordinarily complex and not well understood. Traditional methods of analyzing RNA-sequencing data may not be sufficient for unraveling complicated interactions between viruses and host cells. Using RNA and DNA-sequencing data from The Cancer Genome Atlas (TCGA), we aim to explore whether virus-induced tumors exhibit similar immune-associated (IA) dysregulations using a new algorithm we developed that focuses on the most important biological mechanisms involved in virus-induced cancers. Differential expression, survival correlation, and clinical variable correlations were used to identify the most clinically relevant IA genes dysregulated in 5 virus-induced cancers (HPV-induced head and neck squamous cell carcinoma, HPV-induced cervical cancer, EBV-induced stomach cancer, HBV-induced liver cancer, and HCV-induced liver cancer) after which a mechanistic approach was adopted to identify pathways implicated in IA gene dysregulation. Results: Our results revealed that IA dysregulations vary with the cancer type and the virus type, but cytokine signaling pathways are dysregulated in all virus-induced cancers. Furthermore, we also found that important similarities exist between all 5 virus-induced cancers in dysregulated clinically relevant oncogenic signatures and IA pathways. Finally, we also discovered potential mechanisms for genomic alterations to induce IA gene dysregulations using our algorithm. Conclusions: Our study offers a new approach to mechanism identification through integrating functional annotations and large-scale sequencing data, which may be invaluable to the discovery of new immunotherapy targets for virus-induced cancers.
format	article
author	Lindsay M. Wong Wei Tse Li Neil Shende Joseph C. Tsai Jiayan Ma Jaideep Chakladar Aditi Gnanasekar Yuanhao Qu Kypros Dereschuk Jessica Wang-Rodriguez Weg M. Ongkeko
author_facet	Lindsay M. Wong Wei Tse Li Neil Shende Joseph C. Tsai Jiayan Ma Jaideep Chakladar Aditi Gnanasekar Yuanhao Qu Kypros Dereschuk Jessica Wang-Rodriguez Weg M. Ongkeko
author_sort	Lindsay M. Wong
title	Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach
title_short	Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach
title_full	Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach
title_fullStr	Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach
title_full_unstemmed	Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach
title_sort	analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/42db16df2cf14ea897710911650e674c
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Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach

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