Network analysis reveals critical regulators PTK2, GSK3β, and β-catenin involved in hepatocellular carcinoma progression, suggesting new research directions.
Hepatocellular carcinoma (HCC) is a highly aggressive primary liver cancer with significant morbidity and mortality. The development and progression of HCC involves several genetic mutations, alterations in signaling pathways leading to dysregulation of cellular processes. Several investigations have demonstrated the involvement of diverse regulators and their complex signaling cascades in progression of HCC. Understanding these crucial signaling pathways, including receptor tyrosine pathways, PI3K/AKT/mTOR, Wnt/β-catenin, Ras/Raf/MAPK, TGF-β, Hedgehog, JAK/STAT, and Hippo signaling, offers potential avenues for further experimental explorations and system level studies. The present study aims to construct a comprehensive molecular map of the signaling pathways involved in the development and progression of HCC using network editor Cell Designer. The assembled network, consisting of 193 distinct regulators and 362 reactions, provides a holistic representation of HCC associated pathways and adheres to Systems Biology Graphical Notation (SBGN) format. Through subsequent analysis the crucial regulators such as PTK2, GSK3β, β-catenin, and their pivotal roles in driving HCC progression were illuminated. These findings underscore the potential prognostic and clinical significance of regulators influencing the patient outcomes in HCC. A similar workflow can provide further insights and comprehensive understanding of the disease mechanisms.
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Gottumukkala et al. (2025) studied this question.
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