| الوصف: |
Oro-pharyngeal squamous cell carcinoma (OPSCC) cases are rising worldwide specifically among young individuals with risk factors including smoking and alcohol. HPV infection specifically the subtype HPV16 is a significant risk factor in the initiation and progression of OPSCC, more prevalent in the western part of the world. This study carries out a computational analysis using protein interactions between HPV16 proteins and protein products of key OPSCC and Oral Squamous Cell Carcinoma (OSCC) cancer genes, which aims to investigate the influence of HPV16 on OPSCC and OSCC in terms of protein-protein interactions (PPIs).We created a protein interaction network of HPV16 and human proteins followed by retrieval of mutated genes in OPSCC and OSCC from online databases including COSMIC, cBioPortal and the GDC Portal, along with literature mining. We used MCODE and ClueGo tools for cluster and enrichment analysis, respectively. Drug candidates against the common interacted proteins were found using drug databases like PanDrugs and CLUE Repurposing. After annotating the HPV16-Human PPI network with proteins encoded by genes found to be mutated in both cancers, 31 proteins in OPSCC and 17 proteins in OSCC were in direct interaction with the viral proteins especially, E5, E6, and E7. The immediate network (of first neighbors only) appeared to be sparse, but after looking at the broader HPV16-Human network we found 5 highly connected modules, 4 of which were dominated by proteins encoded by genes mutated in OPSCC as compared to OSCC, indicating the influence of HPV16 on OPSCC. Based on module integrity and topological characteristics we identified 4 significant candidates for HPV16-driven OPSCC i.e. MYC, CREBBP, PML, and RB1 which are significantly enriched in cancer pathways. In the South Asian countries, Epstein Bar Virus type 1 (EBV-1) is a more prevalent risk factor for virus-driven Head and Neck Squamous Cell Carcinoma (HNSCC) as compared to HPV-16, however, knowledge regarding the EBV induced OPSCC and OSCC is scarce. We created a protein interaction network for EBV1 and Human proteins to analyze the topological characteristics especially of proteins encoded by genes mutated in HNSCC using the same methodology and we identified 5 candidate proteins i.e. EP300, CUL3, RB1, DDB1, and CREBBP for further in vitro validation. Citation Format: Arsalan Riaz, Yusra Ilyas, Faisal Khan. Differential analysis of HPV16-human and EBV1-human protein interaction networks to identify new protein candidates in head and neck squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6323. |
