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Eurasian Journal of
Medicine and Oncology Mapping breast cancer PPI networks for targets

4. Discussion pathways, including signal transduction, apoptosis, and
cellular stress responses. 41,42
This study highlights the biological significance of BCPIN
as a structured representation of protein interactions Zones 1 – 3 exhibit a dense core structure enriched
within a metric space. By categorizing proteins into with proteins essential for cellular function and survival,
separate zones according to their graph theoretic distance such as signaling proteins, cell cycle regulators, and
from the core protein MAPK14, our analysis provides a tumor suppressors. The high connectivity in these zones
comprehensive view of the hierarchical organization of supports their functional importance, with these proteins
protein interactions. The findings emphasize the centrality being closely involved in critical pathways like immune
of MAPK14, which is not only topologically central but modulation and cell cycle regulation. Furthermore, the
also functionally essential pathways associated with cancer enrichment of successful drug targets in these central zones
and other diseases. This aligns with previous research underscores their relevance for therapeutic strategies, in
that identifies MAPK14 as a key regulator in oncogenic agreement with the findings of Mukherjee and Zhang and
Zhao et al., 43,44 who reported similar protein clustering
Table 8. The spatial allocation of successful drug target around central nodes in cancer-related networks.
proteins within the BCPIN zones The dense connectivity within zones 1 – 3 reflects the

Zone Protein count Successful drug target proteins (%) Total biological necessity of tightly regulated protein interactions
1 374 34 (9.09) 299 in central cellular processes. The significant presence
of oncogenes and tumor suppressor proteins in these
2 4496 227 (5.01) zones suggests their active role in maintaining cellular
3 2918 37 (1.26) homeostasis and responding to dysregulation, a hallmark
4 249 0 (0) of cancer progression. This finding aligns with the study by
45
5 27 1 (3) Brown et al., which demonstrated that proteins in densely
Abbreviation: BCPIN: Breast cancer protein-protein interaction connected network zones are often critical in disease
network. pathogenesis.
Table 9. Distribution of MAPK signaling and apoptosis‑related proteins

Zone MAPK signaling (%) S/ON (%) S/OFF (%) Apoptosis (%) A/ON (%) A/OFF (%)
1 93 (24.86) 75 (20.05) 57 (15.24) 13 (3.47) 6 (1.60) 4 (1.06)
2 254 (5.64) 373 (8.29) 309 (6.87) 19 (0.42) 13 (0.28) 3 (0.06)
3 34 (1.16) 68 (2.33) 60 (2.05) 4 (0.13) 2 (0.06) 2 (0.06)
4 34 (0.40) 2 (0.80) 0 (0) 0 (0) 0 (0) 0 (0)
5 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
Abbreviations: A/OFF: Negative apoptosis; A/ON: Positive apoptosis; S/OFF: Negative signaling; S/ON: Positive signaling.

Table 10. Functional enrichment in BCPIN core zones
Pathways with significant enrichment Zone 1 (%) Zone 2 (%) Zone 3 (%) Zone 4 (%)
Signal transduction 59.4 35.8 0.0 0.0
Immune system 45 21 11 0.0
Signaling by NGF 25.5 6.8 0.0 0.0
Gene expression 22.2 13.8 18.8 11.3
Hemostasis 20.8 6.9 3.3 0.0
Apoptosis 11.9 2.7 0.0 0.0
Mitotic G1-G1/S phases 8.3 2.1 0.0 0.0
Mitotic G2-G2/M phases 4.4 2.9 0.0 0.0
DNA repair 5.8 3.1 0.0 0.0
p53 signaling 5.8 0.9 0.0 0.0
Notch signaling 3.3 1.2 0.0 0.0

Volume 9 Issue 3 (2025) 80 doi: 10.36922/ejmo.8208