Importantly, ITGB4 has been implicated in modulating cell adhesion through PI3K/AKT signaling and has also been associated with drug resistance in several malignancies, and our findings suggest that targeting ITGB4 may represent a promising strategy to overcome gemcitabine resistance in iCCA, with potential clinical translation in the context of ongoing drug development for CCA (Shi et al., 2022; Fang et al., 2023; Zhu et al., 2025). This evidence concerns the gene AKT1 and cholangiocarcinoma.