Comprehensive Network of Signaling Pathways in Hepatocellular Carcinoma and Network Analysis Reveals PTK2, GSK3β, and β-catenin to be Crucial for Cancer Progression

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/{beta}-catenin, Ras/Raf/MAPK, TGF-{beta}, 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, GSK3{beta}, {beta}-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. Similar workflow can provide further insights and comprehensive understanding of the disease mechanisms. HighlightsO_LIA detailed molecular interaction map of pathways and regulators involved in HCC was developed. C_LIO_LITo illustrate one of the applications of the map developed, topological analysis using Cytoscape was performed to identify the significant hubs. Subsequently, the prognostic relevance of these identified hubs was evaluated using the transcriptome-based analysis. C_LIO_LIThese analysis revealed the crucial roles of regulators like PTK2, GSK3{beta}, and {beta}-catenin offering new prospects for potential prognostic and clinical significance of regulators in influencing HCC. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=65 SRC="FIGDIR/small/666714v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@a0714forg.highwire.dtl.DTLVardef@16f18a1org.highwire.dtl.DTLVardef@ba17b1org.highwire.dtl.DTLVardef@1697432_HPS_FORMAT_FIGEXP M_FIG C_FIG