Page 90 - EJMO-9-2

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

The distinct enrichment patterns across zones reflect the The spatial distribution of pathways across zones
functional hierarchy of the network, with central proteins provides insights into their functional roles. For instance,
(zone 1) acting as master regulators, while peripheral proteins the significant enrichment of the TNF pathway in zone
in the outer zones contribute to less specialized processes. 1 (OR = 4.22) indicates its central role in inflammatory
responses linked to cancer. The PI3K-AKT pathway, while
3.2.3. Statistical significance of OR values dominant in zone 1, extends into outer zones, suggesting

To assess the probability of specific proteins appearing in its involvement in both core and peripheral signaling
a given zone, OR values were calculated based on their processes. In contrast, JAK-STAT, mTOR, and Wnt pathways
distribution across the network (Table 3). The statistical show relatively more stable distributions, suggesting their
significance of these OR values was determined using complementary roles in cancer progression.
95% CIs, which provide a measure of the precision and In summary, the analysis suggests that, in most cases,
reliability. the probability of a protein belonging to a cancer-related
The TNF pathway exhibited an OR of 4.22 (CI: 2.68 – pathway is greater in zone 1 than in zone 2. If these
6.66), indicating that proteins associated with this pathway pathways are particularly relevant to cancer research, the
are approximately 4 times more likely to be found in zone findings indicate that proteins within zone 1 are more
1 than in zone 2. The lower bound of the CI (2.68) being likely to be associated with key oncogenic processes.
well above 1 confirms the statistical significance of this result 3.3. Key proteins driving cancer-related signaling
(p < 0.05), underscoring the TNF pathway’s central role in pathways
the network core and its potential role in cancer progression.
3.3.1. The ten most significant proteins in signaling
In contrast, pathways such as JAK-STAT (OR: 1.17, pathways across various zones
CI: 0.756 – 1.83), mTOR (OR: 1.2, CI: 0.74 – 1.94), and
Wnt (OR: 1.06, CI: 0.67 – 1.69) had ORs close to 1, with To determine the proteins involved in the greatest number
CIs that include 1, suggesting a more even distribution of pathways, the top ten were selected. Each of these
across zones without a statistically significant preference proteins is present in at least three pathways, with all being
for zone 1. Despite the PI3K-AKT pathway’s dominance part of the PI3K and mTOR pathways (Table 4). A value of
in zone 1 (51% of signaling proteins), its OR was 0.87
(CI: 0.6 – 1.29), indicating a slightly lower likelihood of Table 4. Distribution of ten most significant proteins in
being concentrated in zone 1 compared to zone 2, though signaling pathways within zones
this result was not statistically significant. These findings Name of PI3K‑ TNF JAK‑STAT mTOR Wnt Average
highlight the TNF pathway as a statistically significant protein AKT (%)
outlier in zone 1, emphasizing its unique role in the network PRKCA 1 0 0 1 1 60
core. Overall, the TNF pathway stands out as the most
significant differentiating factor between the two zones, SOS2 1 0 1 1 0 60
with its proportion dropping dramatically beyond zone AKT1 1 1 1 1 1 80
3 to approximately 10% (Table 2), while other pathways PIK3CA 1 1 1 1 0 80
exhibit a more consistent distribution across the zones. AKT2 1 1 1 1 0 80
AKT3 1 1 1 1 0 80
Table 3. ORs and confidence intervals for key cancer‑related PIK3CB 1 1 1 1 0 80
pathways PIK3CD 1 1 1 1 0 80

Pathway category OR Confidence interval PIK3R2 1 1 1 1 0 80
Lower Upper PIK3R3 1 1 1 1 0 80
TNF 4.16 2.62 6.6 Abbreviations: PRKCA: Protein kinase C alpha; SOS2: Son of sevenless
JAK-STAT 1.22 0.78 1.91 homolog 2; AKT1: AKT serine/threonine kinase 1;
PIK3CA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit
mTOR 1.26 0.77 2.04 alpha; AKT2: AKT serine/threonine kinase 2; AKT3: AKT serine/threonine
Wnt 1.02 0.64 1.63 kinase 3; PI3KCB: Phosphatidylinositol-4,5-bisphosphate 3-kinase
catalytic subunit beta; PI3KCD: Phosphatidylinositol-4,5-bisphosphate
PI3K-AKT 0.89 0.61 1.31 3-kinase catalytic subunit delta; PIK3R2: Phosphoinositide-3-kinase
Abbreviations: OR: Odds ratio; PI3K-AKT: Phosphatidylinositol regulatory subunit 2; PIK3R3: Phosphoinositide-3-kinase regulatory
3-kinase-protein kinase B; TNF: Tumor necrosis factor; subunit 3; PI3K-AKT: Phosphatidylinositol 3-kinase-protein kinase B;
JAK-STAT: Janus kinase-signal transducer and activator of TNF: Tumor necrosis factor; JAK-STAT: Janus kinase-signal transducer
transcription; mTOR: Mammalian target of rapamycin. and activator of transcription; mTOR: Mammalian target of rapamycin.

Volume 9 Issue 2 (2025) 82 doi: 10.36922/ejmo.8082