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. 2023 Jul:180:106115.
doi: 10.1016/j.micpath.2023.106115. Epub 2023 May 1.

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

S Chatterjee  1 , B S Sanjeev  2
Affiliations

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

S Chatterjee et al. Microb Pathog. 2023 Jul.

Abstract

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 inhibitors (TKI) for further clinical investigations in the inhibition of BCR-mediated EBV activation in carcinomas for better prognostic and therapeutic outcomes.

Keywords: Community detection; Epstein-Barr virus, lymphoma; Louvain method; Tyrosine-protein kinase.

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Conflict of interest statement

Declaration of competing interest All authors have participated in (a) the conception and design or analysis and interpretation of data (b) drafting the article and revising it critically for important intellectual content, and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organisation with a direct or indirect financial interest in the subject matter discussed in the manuscript.

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