Ranking cancer pathways at the core of the protein interaction network: Identifying key signaling protein using the odds ratio test

Understanding the intricate network of cancer pathways within protein-protein interactions (PPIs) presents a considerable challenge. Ranking these pathways by importance is difficult, as their relevance varies depending on cancer type and specific biological context. In this study, a probability odds ratio (OR) test was employed to uncover significant insights into this complexity. PPI networks were analyzed as a metric space to gain insights into their organization and functional architecture. A central protein was identified as the network’s “center,” with other proteins grouped into specific zones according to their proximity to this central point. The analysis focused on the central zones of the network, examining pathways for functional enrichment, investigating molecular mechanisms linked to oncogenes and tumor suppressors, and identifying critical proteins involved in key cellular processes. The findings highlight the importance of central proteins and pathways in driving oncogenesis and offer potential therapeutic targets. The analysis revealed an enrichment of cancer-related pathways, including PI3K-AKT, TNF, JAK-STAT, mTOR, and Wnt, with central zones of the interaction network demonstrating an important role in cancer progression. Zones 1 and 2 showed a dense concentration of cancer-associated pathways, highlighting the critical roles of core proteins in signaling and functional interactions essential to tumor biology. Among the pathways, the PI3K-AKT pathway was dominant in zone 1, accounting for approximately 51% of signaling proteins. The TNF pathway exhibited a distinct pattern, with an OR of 4.22, indicating its higher concentration in zone 1 compared to zone 2. In contrast, pathways such as JAK-STAT, mTOR, and Wnt showed more stable distributions across zones but exhibited slightly lower ORs. Importantly, ten proteins emerged as key players, central to multiple pathways and crucial for cancer progression, cell survival, and metabolism. These proteins – PRKCA, SOS2, AKT1, PIK3CA, AKT2, AKT3, PIK3CB, PIK3CD, PIK3R2, and PIK3R3 – are closely associated with oncogenic processes. Each contributes to cell proliferation, survival, and differentiation, with functional implications across various cancer types, including lung cancer. Understanding the roles of these proteins within the broader cancer pathway network deepens knowledge of tumor biology and opens new possibilities for the development of novel therapeutic approaches.