Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach.
Comput Struct Biotechnol J
; 19: 6240-6254, 2021.
Article
em En
| MEDLINE
| ID: mdl-34900135
ABSTRACT
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.
Algorithm; C2, Canonical pathway; C6, Oncogenic signature; C7, Immunological signature; CA, Cancer-associated; CESC, Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma; CNA, Copy number alteration; Cervical squamous cell carcinoma and endocervical adenocarcinoma; EBV, Epstein-Barr virus; Epstein-Barr virus; FDR, False discovery rate; GSEA, Gene set enrichment analysis; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HNSCC, Head and Neck Squamous Cell Carcinoma; HPV, Human papillomavirus; Head and neck squamous cell carcinoma; Hepatitis B; Hepatitis C; Human papillomavirus; IA, Immune-associated; LIHC, Liver Hepatocellular Carcinoma; Liver hepatocellular carcinoma; MSigDB, Molecular Signature Database; STAD, Stomach Adenocarcinoma; Stomach adenocarcinoma; TCGA; TCGA, The Cancer Genome Atlas
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Comput Struct Biotechnol J
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos