AccScience Publishing / EJMO / Online First / DOI: 10.36922/ejmo.8082
ORIGINAL RESEARCH ARTICLE

Ranking cancer pathways at the core of the protein interaction network: Identifying key signaling protein using the odds ratio test

Emad Fadhal1,2* Neji Saidi1,3
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1 Department of Mathematics and Statistics, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia
2 Department of Mathematics and Applied Mathematics, University of the Western Cape, Private Bag X17, Bellville, South Africa
3 Higher Institute of Informatics in Kef (ISIK), University of Jendouba, Tunisia
Received: 19 December 2024 | Revised: 23 January 2025 | Accepted: 8 February 2025 | Published online: 26 February 2025
© 2025 by the Auhor(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Understanding the intricate network of cancer pathways within protein-protein interactions (PPIs) presents a considerable challenge. Ranking these pathways by importance is difficult, as their relevance varies depending on cancer type and specific biological context. In this study, a probability odds ratio (OR) test was employed to uncover significant insights into this complexity. PPI networks were analyzed as a metric space to gain insights into their organization and functional architecture. A central protein was identified as the network’s “center,” with other proteins grouped into specific zones according to their proximity to this central point. The analysis focused on the central zones of the network, examining pathways for functional enrichment, investigating molecular mechanisms linked to oncogenes and tumor suppressors, and identifying critical proteins involved in key cellular processes. The findings highlight the importance of central proteins and pathways in driving oncogenesis and offer potential therapeutic targets. The analysis revealed an enrichment of cancer-related pathways, including PI3K-AKT, TNF, JAK-STAT, mTOR, and Wnt, with central zones of the interaction network demonstrating an important role in cancer progression. Zones 1 and 2 showed a dense concentration of cancer-associated pathways, highlighting the critical roles of core proteins in signaling and functional interactions essential to tumor biology. Among the pathways, the PI3K-AKT pathway was dominant in zone 1, accounting for approximately 51% of signaling proteins. The TNF pathway exhibited a distinct pattern, with an OR of 4.22, indicating its higher concentration in zone 1 compared to zone 2. In contrast, pathways such as JAK-STAT, mTOR, and Wnt showed more stable distributions across zones but exhibited slightly lower ORs. Importantly, ten proteins emerged as key players, central to multiple pathways and crucial for cancer progression, cell survival, and metabolism. These proteins – PRKCA, SOS2, AKT1, PIK3CA, AKT2, AKT3, PIK3CB, PIK3CD, PIK3R2, and PIK3R3 – are closely associated with oncogenic processes. Each contributes to cell proliferation, survival, and differentiation, with functional implications across various cancer types, including lung cancer. Understanding the roles of these proteins within the broader cancer pathway network deepens knowledge of tumor biology and opens new possibilities for the development of novel therapeutic approaches.

Keywords
Cancer pathways
Protein interaction networks
Therapeutic targets
Odds ratio analysis
Lung cancer progression
PI3K-AKT signaling
Funding
Faculty of Natural Science research office at University of the Western Cape.
Conflict of interest
The authors declare no conflicts of interest.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing