Page 92 - EJMO-9-2

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

regulatory subunit 3 (PIK3R3) regulates PI3K activity and survival, and differentiation. These proteins not only
is associated with tumorigenesis, particularly in breast and play vital roles in oncogenic processes but also represent
lung cancers. 38 promising targets for therapeutic intervention, particularly
The distinct enrichment of pathways across zones also in lung cancer.
provides insights into the hierarchical organization of The identification of key signaling proteins and
the PPI network. Proteins in zone 1 function as central pathways within the core of the protein interaction network
nodes, facilitating critical interactions, whereas proteins provides a strong foundation for further investigation.
in the outer zones may have more redundant functions. Future studies will focus on experimentally validating
This spatial distribution aligns with the concept of “core- the biological functions and roles of these ten identified
periphery” structure in biological networks, where central proteins in cancer progression through both in vitro and
(core) nodes integrate diverse signals, and peripheral in vivo models, assessing their impact on cell proliferation,
nodes contribute to specific processes. 39 survival, and metastasis. In addition, efforts will be
Moreover, the slight variations in ORs for pathways directed toward developing biomarkers for early cancer
like JAK-STAT, mTOR, and Wnt across zones suggest detection and personalized therapeutic strategies based on
subtle roles in different stages of cancer progression. These the identified signaling proteins and pathways.
pathways may represent complementary therapeutic The findings from this study offer a strategic framework
targets, and their inhibition, when combined with central for targeted therapies, emphasizing the potential to disrupt
pathway inhibitors, could produce synergistic therapeutic cancer progression by targeting central signaling hubs. By
effects.
refining the understanding of pathway interactions and
This study lays the foundation for integrating network protein roles, this study paves the way for advancements in
centrality metrics with functional annotations to refine cancer treatment strategies.
drug discovery strategies. Prioritizing pathways and
proteins based on their network centrality and enrichment Acknowledgments
can simplify the identification of viable therapeutic targets. None.
Finally, the enrichment of critical cancer pathways and
key signaling proteins within the network core highlights Funding
their fundamental roles in tumor biology. These findings This work was supported by the Faculty of Natural Science
not only deepen the understanding of cancer progression Research Office at University of the Western Cape. The
but also pave the way for developing targeted therapies opinions and conclusions expressed are those of the author
aimed at disrupting central signaling hubs. and should not necessarily be attributed to the research
5. Conclusion office.

This study maps a path through the complexity of Conflict of interest
cancer-related protein interaction networks, uncovering The authors declare no conflicts of interest.
key insights into pathway enrichment and functional
importance within the core zones of the network. Using Author contributions
the OR test, cancer-centric pathways, such as PI3K-
AKT, TNF, JAK-STAT, mTOR, and Wnt, were identified Conceptualization: Emad Fadhal
with the highest concentrations in zones 1 and 2, where Data curation: Emad Fadhal
signaling proteins crucial to tumor progression are Formal analysis: All authors
densely clustered. The PI3K-AKT pathway, particularly Investigation: All authors
dominant in zone 1, emerged as a critical driver, Methodology: All authors
constituting over half of the core signaling proteins. Writing – original draft: All authors
Meanwhile, the TNF pathway displayed a uniquely high Writing – review & editing: Emad Fadhal
OR, highlighting its role in inflammation and its link to
cancer. Ethics approval and consent to participate

This analysis identifies ten pivotal proteins (PRKCA, Not applicable.
SOS2, AKT1, PIK3CA, AKT2, AKT3, PIK3CB, PIK3CD, Consent for publication
PIK3R2, and PIK3R3) positioned at the intersection of key
pathways, with broad implications for cell proliferation, Not applicable.

Volume 9 Issue 2 (2025) 84 doi: 10.36922/ejmo.8082