Integrated single-cell and bulk RNA sequencing analysis identifies a pyroptosis related prognostic model for predicting prognosis and therapeutic response in intrahepatic cholangiocarcinoma.

Intrahepatic Cholangiocarcinoma (iCCA) is the second most common aggressive liver malignancy. The heterogeneous nature of iCCA poses a serious challenge for prognostic prediction and individualized therapy. Pyroptosis, a novel programmed cell death, has recently been implicated in the development and treatment of human cancers. However, its clinical significance in iCCA is unclear. Single-cell sequencing data was analyzed to uncover the transcriptomic heterogeneity, intercellular crosstalk, and pyroptosis levels of iCCA cells. A pyroptosis-related prognostic model was constructed, and the prognostic efficiency was validated in an external cohort. Five iCCA cell clusters were identified. Cluster1 with the highest pyroptosis score showed an intimate cell-cell communication with cluster3 that represented acute inflammatory response activity. Pyroptosis genes along pseudotime showed distinguishable distribution among three subtypes in cluster1. Risk score was proved as an independent prognostic factor. High-risk patients demonstrated high TMB, MSI-H phenotype, and poorer survival. Tumor immune infiltration characteristics and chemotherapeutics response demonstrated difference in the two risk groups. Targeted drug tanespimycin was positively correlated with hub gene BNIP3, and refametinib and crizotinib showed negative association with JUN. The pyroptosis-related model demonstrated potential in predicting prognosis and individualized therapy strategies.