Community detection in Epstein-Barr virus associated carcinomas and role of tyrosine kinase in etiological mechanisms for oncogenesis

Background: Epstein-Barr virus (EBV) affects more than 90% of global population. The role of the virus in causing infectious mononucleosis (IM) affecting B-cells and epithelial cells and in the development of EBV associated cancers is well documented. Investigating the associated interactions can pave way for the discovery of novel therapeutic targets for EBV associated lymphoproliferative (Burkitt's Lymphoma and Hodgkin's Lymphoma) and non-lymphoproliferative diseases (Gastric cancer and Nasopharyngeal cancer).Methods: Based on the DisGeNET (v7.0) data set, we constructed a disease-gene network to identify genes that are involved in various carcinomas, viz. Gastric cancer (GC), Nasopharyngeal cancer (NPC), Hodgkin's lymphoma (HL) and Burkitt's lymphoma (BL). We identified communities in the disease-gene network and performed functional enrichment using over-representation analysis to detect significant biological processes/pathways and the interactions between them.Result: We identified the modular communities to explore the relation of this common causative pathogen (EBV) with different carcinomas such as GC, NPC, HL and BL. Through network analysis we identified the top 10 genes linked with EBV associated carcinomas as CASP10, BRAF, NFKBIA, IFNA2, GSTP1, CSF3, GATA3, UBR5, AXIN2 and POLE. Further, the tyrosine-protein kinase (ABL1) gene was significantly over-represented in 3 out of 9 critical biological processes, viz. in regulatory pathways in cancer, the TP53 network and the Imatinib and chronic myeloid leukemia biological processes. Consequently, the EBV pathogen appears to target critical pathways involved in cellular growth arrest/apoptosis. We make our case for BCR-ABL1 tyrosine-kinase in-hibitors (TKI) for further clinical investigations in the inhibition of BCR-mediated EBV activation in carcinomas for better prognostic and therapeutic outcomes.

Automated summary

By constructing a disease-gene network, the relationship between Epstein-Barr virus (EBV) and different types of cancers (Gastric cancer, Nasopharyngeal cancer, Hodgkin's lymphoma and Burkitt's lymphoma) was investigated, and important genes associated with EBV were identified. Through functional enrichment analysis, it was found that EBV affects critical pathways related to cellular growth arrest/apoptosis. Therefore, BCR-ABL1 tyrosine kinase inhibitors may have potential clinical applications in inhibiting BCR-mediated EBV activation.