Deconstruction of the immune microenvironment identifies tumor-, immune- and stroma-specific subtypes of intrahepatic cholangiocarcinoma

We have profiled by RNA-sequencing healthy livers and 4 distinct murine intrahepatic cholangiocarcinoma (iCCA) models to compare their molecular profile to the identified human STIM clusters of iCCA. Results: Comparative analysis indicated high molecular similarity between the KRAS/p19 model and the human Inflammatory stroma cluster while the other models resembled the Hepatic stem-like cluster. Livers from healthy mice, and from mice injected with 4 distinct plasmids combinations (KRAS/p19, NICD1/AKT1, YAP1/AKT1 and FBXW7/AKT1) were collected in triplicates and processed for RNA extraction and subsequent RNA-sequencing. Molecular class prediction, single sample enrichment analysis and Deseq analysis were performed to compare the murine tumors to the human disease and to the 5 proposed human clusters.