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Abstract Introduction Cross‐talk among biological pathways is essential for normal biological function and plays a significant role in cancer progression. Through integrated network analysis, this study explores the significance of pathway cross‐talk in colorectal cancer (CRC) development at both the pathway and gene levels. Methods In this study, we integrated the gene expression data with domain knowledge to construct state‐dependent pathway cross‐talk networks. The significance of the genes involved in pathway cross‐talk was assessed by analyzing their association with cancer hallmarks, disease‐gene relation, genetic alterations, and survival analysis. We also analyzed the gene regulatory network to identify the dysregulated genes and their role in CRC progression. Results Cross‐talk was observed between immune‐related pathways and pathways associated with cell communication and signaling. The PTPRC gene was identified as a mediator, facilitating interactions within the immune system and other signaling pathways. The rewired interactions of ITGA7 were identified as influential in the epithelial‐mesenchymal transition in CRC. This study also highlighted the crucial link between cell communication and vascular smooth muscle contraction pathway in CRC progression. The survival analysis of identified gene clusters showed their significant prognostic value in distinguishing high‐risk from low‐risk CRC groups, and L1000CDS2 revealed seven potential drug molecules in CRC. Nine dysregulated genes (CTNNB1, EP300, JUN, MYC, NFKB1, RELA, SP1, STAT1, and TP53) emerge as transcription factors acting as common regulators across various pathways. Conclusions This study highlights the crucial role of pathway cross‐talk in CRC progression and identified the potential prognostic biomarkers and potential drug molecules.
Mahajan et al. (Sat,) studied this question.