ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma.

Ferroptosis is a recently discovered mode of cell death that inhibits tumor growth. Single-cell RNA sequencing (scRNA-seq) is a powerful tool for analyzing tumor heterogeneity and the immune microenvironment at the single-cell level. We used CIBERSORT to identify cellular immune scores and found that monocytes had significantly infiltrated and were correlated with prognosis in cholangiocarcinoma. scRNA-seq data were extracted from the Gene Expression Omnibus database, and the FindCluster() package was used for cell cluster analysis, which obtained 21 cell clusters, and there was increased TNFSF13B-TFRC intercellular communication between monocytes and cholangiocytes. A weighted correlation network analysis was performed with the WGCNA package to obtain monocyte-related gene modules. Univariate and multivariate Cox analyses were then performed to further establish the signature, and the reliability of the signature was assessed by receiver operating characteristic curve and decision curve analysis. A nomogram signature based on the Kaplan-Meier survival analysis was established. We found that the communication between monocytes and malignant cells in cholangiocarcinoma may be a regulatory factor of ferroptosis in cancer cells. The prognostic stratification system of the three-gene signature related to monocytes and ferroptosis can accurately assess the prognostic risk for cholangiocarcinoma.