Page 89 - EJMO-9-2

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

cancer pathways were more prevalent in zone 1 compared interactions across various zones revealed that about half
to zone 2. of the proteins in each zone are part of the PI3K pathway
In biomedical trials with dichotomous outcomes, effect (Table 2). Conversely, the mTOR pathway has the fewest
measures are typically derived by comparing risks or odds associated proteins in zone 1, while the TNF pathway is
between two intervention groups. These comparisons can least represented in the zone 2.
be expressed as ratios (risk ratio or OR) or as differences in 3.2.2. Significance of zones in cancer progression
risk (risk difference).
The central zones (zones 1 and 2) are enriched with proteins
Risk is defined as the probability of a specific event involved in critical signaling pathways implicated in cancer,
or outcome occurring, calculated as the number of including PI3K-AKT, TNF signaling, JAK-STAT, mTOR,
occurrences of the outcome of interest divided by the total and Wnt pathways. These zones act as hubs for signal
number of possible outcomes. The term odds are frequently transduction and functional interactions essential for tumor
used interchangeably with risk, though it specifically refers progression. Zone 1 contains the highest concentration of
to the ratio of the probability of an event occurring to PI3K-AKT pathway-related proteins (51%), highlighting its
the probability of it not occurring. Odds and risks can be role as a central regulator of cell survival and proliferation.
interconverted using the formula: odds = risk/(1 − risk). 22 Zone 2 shows a lower but remains significantly enriched
In this study, the odds represent the ratio of the with cancer pathways, suggesting a secondary role in
probability of proteins being associated with a specific modulating signaling cascades.
pathway to the probability of proteins not being associated
with that pathway. This is expressed as p/(1−p), where p is Table 1. Distribution of proteins associated with signaling
the probability of a protein belonging to the pathway, also pathways across different zones
referred to as the risk. Pathway category Zone 1 (%) Zone 2 (%)
The OR is a statistical measure used to quantify the PI3K-AKT 68 (18.18) 244 (5.29)
strength of association between two events: event A TNF 46 (12.29) 51 (1.10)
(a protein belonging to a specific pathway) and event B (the JAK-STAT 35 (9.35) 105 (2.27)
protein being located in a particular zone of the network). mTOR 28 (7.48) 79 (1.71)
3. Results Wnt 29 (7.75) 97 (2.10)
Abbreviations: PI3K-AKT: Phosphatidylinositol 3-kinase-protein
3.1. Identification of core cancer pathways in the PPIN kinase B; TNF: Tumor necrosis factor; JAK-STAT: Janus kinase-signal
Earlier studies employed a distinctive approach involving transducer and activator of transcription; mTOR: Mammalian target of
the calculation of metric space to categorize proteins and rapamycin.
allocate them to specific zones based on their proximity to the Table 2. Descriptive statistics for signaling pathways related
network’s center. In this study, a 9448-protein network was proteins within zones
17
analyzed and segmented into six distinct zones such as 374,
4610, 3464, 578, 14, and 2 proteins, respectively. Enrichment Zone Number of proteins Pathway category P Odds
analyses were subsequently performed on these zones using Zone 1 133 PI3K-AKT 0.51 1.04
comparative toxicogenomic databases and gene ontology term TNF 0.345 0.528
enrichment analysis, encompassing gene set enrichments. JAK-STAT 0.26 0.357
23
The findings revealed that among the six zones in the network, mTOR 0.21 0.266
zone 1 and zone 2 exclusively housed the critical pathways in
cancer, including PI3K-AKT, TNF, JAK-STAT, mTOR, and Wnt 0.22 0.278
Wnt signaling pathway (Table 1). This observation led to the Zone 2 453 PI3K-AKT 0.538 1.167
classification of cancer pathways within the core of the PPIN, TNF 0.11 0.126
aiming to identify key signaling proteins. JAK-STAT 0.225 0.29
3.2. Zonal distribution of cancer-related signaling mTOR 0.174 0.211
pathways Wnt p 0.214 0.272
3.2.1. Comparison of proteins related to signaling Notes: p=belonging probability; Odds = 1− p .
pathways across different zones Abbreviations: PI3K-AKT: Phosphatidylinositol 3-kinase-protein
kinase B; TNF: Tumor necrosis factor; JAK-STAT: Janus kinase-signal
The proteins linked to signaling pathways in various transducer and activator of transcription; mTOR: Mammalian target of
zones were examined. A descriptive analysis of protein rapamycin.

Volume 9 Issue 2 (2025) 81 doi: 10.36922/ejmo.8082