Page 86 - EJMO-9-2

Eurasian Journal of Medicine
and Oncology

ORIGINAL RESEARCH ARTICLE
Ranking cancer pathways at the core of the

protein interaction network: Identifying key
signaling protein using the odds ratio test

Emad Fadhal * and Neji Saidi 1,3
1,2
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

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
*Corresponding author: architecture. A central protein was identified as the network’s “center,” with other
Emad Fadhal proteins grouped into specific zones according to their proximity to this central point.
(efadhal@kfu.edu.sa) The analysis focused on the central zones of the network, examining pathways for
Citation: Fadhal E, Saidi N. functional enrichment, investigating molecular mechanisms linked to oncogenes
Ranking cancer pathways at the and tumor suppressors, and identifying critical proteins involved in key cellular
core of the protein interaction processes. The findings highlight the importance of central proteins and pathways
network: Identifying key signaling
protein using the odds ratio test. in driving oncogenesis and offer potential therapeutic targets. The analysis revealed
Eurasian J Med Oncol. an enrichment of cancer-related pathways, including PI3K-AKT, TNF, JAK-STAT, mTOR,
2025;9(2):78-86. and Wnt, with central zones of the interaction network demonstrating an important
doi: 10.36922/ejmo.8082
role in cancer progression. Zones 1 and 2 showed a dense concentration of cancer-
Received: December 19, 2024 associated pathways, highlighting the critical roles of core proteins in signaling and
1st revised: December 21, 2024 functional interactions essential to tumor biology. Among the pathways, the PI3K-
AKT pathway was dominant in zone 1, accounting for approximately 51% of signaling
2nd revised: January 23, 2025 proteins. The TNF pathway exhibited a distinct pattern, with an OR of 4.22, indicating
Accepted: February 8, 2025 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
Published online: February 26,
2025 exhibited slightly lower ORs. Importantly, ten proteins emerged as key players, central
to multiple pathways and crucial for cancer progression, cell survival, and metabolism.
Copyright: © 2025 Author(s). These proteins – PRKCA, SOS2, AKT1, PIK3CA, AKT2, AKT3, PIK3CB, PIK3CD, PIK3R2,
This is an Open-Access article
distributed under the terms of the and PIK3R3 – are closely associated with oncogenic processes. Each contributes to cell
Creative Commons Attribution proliferation, survival, and differentiation, with functional implications across various
License, permitting distribution, cancer types, including lung cancer. Understanding the roles of these proteins within
and reproduction in any medium, the broader cancer pathway network deepens knowledge of tumor biology and
provided the original work is
properly cited. opens new possibilities for the development of novel therapeutic approaches.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Cancer pathways; Protein interaction networks; Therapeutic targets; Odds
regard to jurisdictional claims in
published maps and institutional ratio analysis; Lung cancer progression; PI3K-AKT signaling
affiliations.

Volume 9 Issue 2 (2025) 78 doi: 10.36922/ejmo.8082