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

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

Computational and Structural Biotechnology Journal (Jan 2021)

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

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

Affiliations

Lindsay M. Wong: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Wei Tse Li: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Neil Shende: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Joseph C. Tsai: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Jiayan Ma: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Jaideep Chakladar: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Aditi Gnanasekar: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Yuanhao Qu: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Kypros Dereschuk: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Jessica Wang-Rodriguez: Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA; Pathology Service, VA San Diego Healthcare System, San Diego, CA 92161, USA
Weg M. Ongkeko: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA; Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA; Corresponding author at: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA 92093, USA.

Journal volume & issue: Vol. 19
pp. 6240 – 6254

Abstract

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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.

Published in Computational and Structural Biotechnology Journal

ISSN: 2001-0370 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Technology: Chemical technology: Biotechnology
Website: https://www.journals.elsevier.com/computational-and-structural-biotechnology-journal

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