Page 86 - EJMO-9-3

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

two-step distance to the second zone, and so forth. The essential proteins in each zone, with higher proportions in
analyzed BCPIN comprised 8079 proteins and 163,199 central zones.
interactions. Through this modeling, MAPK14 emerged Table 3 presents the distribution of signaling proteins
as the central protein, highlighting its significant across BCPIN zones. These proteins are predominantly
involvement in various diseases, including cancer concentrated in the core, accounting for 75.13%, 43.37%,
and cardiovascular conditions. Studies indicate that and 16.96% in zones 1, 2, and 3, respectively. The MAPK
24
competing endogenous RNA can promote breast cancer signaling pathway is a known target for cancer treatment.
28
25
progression by modifying the MAPK signaling pathway. Protein kinases play an essential role in regulating cellular
In addition, elevated MAPK14 levels have been detected functions and controlling proliferation, and are considered
in gastric cancer, suggesting its potential as a biomarker key drug targets. This table details the presence of
29
and pharmacological target. Table 1 summarizes the signaling proteins across network zones, emphasizing their
26
node distribution and average connectivity relative to the enrichment in the core.
BCPIN center.
Further analysis examined the spatial allocation
The network has a diameter (the shortest path length
connecting the two most distant nodes in a graph) of of growth-related, cell cycle, tumor suppressor, and
oncogenic proteins (Tables 4-7). The distribution of
9, with the farthest zone from the center being zone 5.
The central protein interacts with 374 proteins in zone growth-related proteins is lowest in the core zone but
1, which has a maximum degree of 531, surpassing the increases in the outer zones. Cell cycle proteins are most
center itself. Zones 1 – 3 contain 96% of all proteins, with concentrated in zones 1 and 2, supporting their role
in regulating tumor growth and progression. Tumor
30
average degrees of 83.62% (zone 1), 28.71% (zone 2), and suppressor and oncogene proteins are mostly found in
56.57% (zone 3). The average degrees for zones 4 and 5 are
1.69% and 1.1%, respectively. Zone 1 proteins interact with zones 1 – 3, aligning with their involvement in cancer
31-34
4,496 zone 2 proteins, comprising over 50% of proteins in development. Table 4 presents the abundance of
both zones. Zone 3 has 2,918 proteins, while zones 4 and growth-related proteins in each zone, demonstrating
5 contain 249 and 27 proteins, respectively. The network their localization near the center. The spatial allocation
structure consists of a dense core and a sparse periphery, of cell cycle-related proteins, as depicted in Table 5, also
with proteins near the topological center exhibiting higher highlights their higher density in central zones. Regarding
connectivity. the concentration of tumor suppressors for each zone.
3.2. Distribution of key proteins in the BCPIN Table 2. The spatial allocation of essential proteins within
network the BCPIN zones
Table 2 categorizes essential proteins within BCPIN zones. Zone Protein count Essential proteins (%) Total
Human proteins crucial for survival, as inferred from 1 374 161 (43.08) 1481
orthologous knockout studies in mice, are predominantly 2 4496 972 (42.61)
27
located in the central zones. Specifically, 43.08%, 42.61%,
and 11.08% of essential proteins reside in zones 1, 2, and 3 2918 329 (11.08)
3, while zones 4 and 5 contain only 6.82% and 7.40%, 4 249 17 (6.82)
respectively. This table highlights the concentration of 5 27 2 (7.40)
Abbreviation: BCPIN: Breast cancer protein-protein interaction
Table 1. A description of how nodes and their connections network.
are arranged starting from the core of the BCPIN network
Table 3. The spatial allocation of signaling proteins within
Zone Protein Average Maximum Minimum the BCPIN zones
count connectivity connectivity connectivity
Center 1 374 374 0 Zone Protein count Signaling proteins (%) Total
1 374 83.62 531 2 1 374 281 (75.13) 2756
2 4496 28.71 409 1 2 4496 1950 (43.37)
3 2918 56.57 393 1 3 2918 495 (16.96)
4 249 1.69 10 1 4 249 28 (11.24)
5 27 1.1 3 1 5 27 2 (7.40)
Abbreviation: BCPIN: Breast cancer protein-protein interaction Abbreviation: BCPIN: Breast cancer protein-protein interaction
network. network.

Volume 9 Issue 3 (2025) 78 doi: 10.36922/ejmo.8208