Abstract
Intrahepatic cholangiocarcinoma (ICC) is a relatively rare but highly aggressive tumour type that responds poorly to chemotherapy and immunotherapy. Comprehensive molecular characterization of ICC is essential for the development of novel therapeutics. We performed a comprehensive multi-omics analysis of ICC via proteomic, whole-exon sequencing (WES) and single-cell RNA sequencing (scRNA-seq). We identified three molecular subtypes with deteriorating prognosis in ICC: chromatin remodelling, metabolism, and inflammation. The inflammation subtype was associated with a poor prognosis. Our random forest algorithm revealed that the mutation of KMT2D frequently occurred in the metabolism subtype and were associated with lower inflammatory activity. scRNA-seq further identified a novel APOE+C1QB+ macrophage subtype, which showed the capacity of promoting the inflammation subtype and contributing to a poor prognosis in ICC. Taking together, with a single-cell transcriptome-assisted multi-omics analysis, we identified novel molecular subtypes of ICC and valided APOE+C1QB+ TAMs as potential novel immunotherapy targets against ICC.
Novel Molecular Subgroups of Intrahepatic Cholangiocarcinoma Discovered by Single-Cell RNA Sequencing-Assisted Multi-Omics Analysis
