"Computational Identification of Actomyosin-Integrin Crosstalk in Gallbladder Cancer Reveals Licoflavone B as a Putative Candidate for Experimental Evaluation"

As the most prevalent biliary tract cancer, gallbladder cancer (GBC) is often identified late, resulting in poor clinical prognosis. Chronic inflammation, and associated abnormalities in smooth muscle contractility and gallbladder motility are increasingly implicated in gallbladder cancer progression, yet their underlying molecular mechanisms remain poorly defined. In the present study, an integrative bioinformatics and in silico framework was applied to identify key molecular drivers and explore potential therapeutic candidates for GBC. Analysis of publicly available GBC RNA-sequencing datasets revealed MYH11 and ITGB5 as key hub genes associated with smooth muscle functioning, extracellular matrix interaction, cytoskeletal organization, and focal adhesion signalling in gallbladder cancer, within the analysed GEO datasets, MYH11 demonstrated strong preliminary diagnostic performance (AUC = 0.909). Both genes converged on pathways linked to epithelial–mesenchymal transition, tumour invasion, and TGF-β–associated signalling, reinforcing their potential relevance to inflammation-driven GBC progression. To assess therapeutic relevance, a panel of plant derived natural compounds with reported roles in gallbladder diseases was screened against MYH11 and ITGB5 via molecular docking. Licoflavone B, a bioactive flavonoid isolated from Glycyrrhiza glabra , emerged as a notable putative candidate, demonstrating favourable predicted binding interactions with both targets, particularly for the MYH11–Licoflavone B interaction, suggesting that this compound may modulate actomyosin contractility and integrin-mediated adhesion signalling in ways relevant to progression in GBC. To our knowledge, this is the first study to investigate Licoflavone B as a candidate molecule in gallbladder cancer. While the findings are computational in nature and require experimental confirmation, they provide a biologically coherent rationale for prioritizing MYH11, ITGB5, and Licoflavone B in future in vitro and in vivo studies aimed at advancing therapeutic strategies for this difficult to treat malignancy.