Page 87 - EJMO-9-2

Eurasian Journal of Medicine and
Oncology
Cancer pathway ranking through odds ratios

1. Introduction therapies. Similarly, the Wnt signaling pathway, which
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regulates stem cell maintenance and differentiation, has
The ambiguous relationship between cancer and been linked to cancer metastasis and drug resistance
protein-protein interactions (PPIs) has been a focus of when aberrantly activated. The identification of critical
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biomedical research for decades, as understanding this proteins within these pathways can pave the way for
relationship is crucial for identifying key drivers of cancer the development of novel targeted therapies that can
progression and potential therapeutic targets. In recent effectively disrupt oncogenic signaling and inhibit cancer
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years, the development of high-throughput techniques cell survival and proliferation.
has significantly enhanced the ability to map human
protein- PPI networks (PPINs), offering insights into One of the most promising approaches in cancer
the molecular underpinnings of cancer. PPIs constitute research is the integration of PPINs with high-throughput
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an extensive network of molecular interactions that data, allowing for a comprehensive understanding of how
play essential roles in maintaining cellular homeostasis, protein interactions regulate cellular processes in both
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regulating gene expression, and facilitating cellular healthy and diseased. Advanced techniques such as
responses to environmental signals. Aberrations in affinity purification coupled with mass spectrometry and
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these interactions often contribute to the uncontrolled yeast two-hybrid screening have enabled the identification
proliferation and apoptosis evasion characteristic of of novel PPIs. In addition, network-based approaches,
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cancerous cells. A critical aspect of understanding including graph theory and statistical tools, are increasingly
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cancer biology involves the identification of key signaling being employed to analyze the structural and functional
proteins within these networks, as they serve as potential properties of these networks. Such approaches enable the
biomarkers for early detection and therapeutic targets. 5 identification of protein modules or clusters of proteins
that are tightly interconnected and may function together
The human PPIN is an intricate system comprising
thousands of proteins that interact with each other to within the same cellular process or pathway. Uncovering
these modules can lead to the discovery of novel drug
regulate cellular functions such as signaling, growth, targets and biomarkers, advancing cancer diagnosis and
metabolism, and immune response. Protein interactions prediction.
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are fundamental to cellular decision-making processes
that control key events like proliferation, differentiation, A powerful tool in network analysis is the odds ratio
and survival. Dysregulation of these networks can lead (OR) test, which provides a robust statistical framework
to cancer development, progression, and metastasis. for assessing the enrichment of differentially, expressed
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Understanding how proteins interact within this complex proteins within specific pathways or protein modules.
network and identifying central nodes – proteins that are The OR test quantifies the strength of association between
highly interconnected or pivotal in signal transduction a given protein and a cancer-related pathway, allowing
– can provide insights into the molecular mechanisms researchers to prioritize proteins based on their likelihood
driving cancer. These central nodes, often termed of involvement in cancer progression. By combining the OR
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“master regulators,” influence essential cellular processes test with network analysis, cancer pathways can be ranked
by regulating the expression of numerous target genes. according to their relevance to tumorigenesis, highlighting
A central hypothesis in cancer research is that master those most likely to contain key signaling proteins.
regulators serve as promising targets for drug development, This approach allows for a more focused and systematic
given their involvement in multiple aspects of cancer investigation of cancer-related pathways, providing a clear
biology, including cell cycle regulation, apoptosis, and roadmap for further experimental validation.
DNA repair. 9 The primary aim of this study is to identify key signaling
Within the PPIN, several signaling pathways have proteins that play crucial roles in cancer progression by
emerged as critical regulators of cancer progression. Key ranking cancer pathways within the core of the protein
pathways such as PI3K-AKT, mTOR, Wnt, and JAK-STAT interaction network using the OR test. By focusing on the
play fundamental roles in regulating cell proliferation, central nodes within the PPIN, a deeper understanding
survival, metabolism, and invasion, all of which are of the essential signaling pathways that drive cancer
hallmark features of cancer cells. 10-13 Dysregulation of these biology is expected to be achieved. The OR test serves
pathways is often implicated in tumorigenesis, making as a guiding framework to prioritize these pathways,
them prime targets for therapeutic intervention. For enabling the discovery of novel cancer-related proteins
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instance, the PI3K-AKT pathway is frequently activated that may function as biomarkers or therapeutic targets.
in many cancers and is associated with poor prognosis, This approach offers a comprehensive framework for
highlighting its potential as a target for precision identifying critical components within the cancer network,

Volume 9 Issue 2 (2025) 79 doi: 10.36922/ejmo.8082