Integrative analysis of scRNA-seq and RNA-seq to investigate the prognostic value of lactylation and fibroblast-related genes in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICCA), the second most prevalent primary liver cancer, is linked to a poor prognosis. However, the role of histone lactylation-related epigenetic modifications in ICCA remains poorly understood. This study aimed to identify reliable prognostic biomarkers and establish a foundation for targeted therapies. Specifically, this study integrated single-cell RNA sequencing (scRNA-seq), bulk transcriptomic data from TCGA-ICCA and GSE107943, and a curated list of histone lactylation-related genes. Cell–cell communication analysis revealed a significant CXCL12–CXCR4 interaction between apCAFs and vCAFs (p < 0.01). Prognostic markers were identified through regression models, and a risk signature was developed and validated using ROC curves. Five genes—STMN1, UBE2T, CENPF, C5orf34, and FAM72C—were established as prognostic indicators. FAM72C exhibited a negative correlation with plasmacytoid dendritic cells (cor = − 0.355), while CENPF correlated negatively with mast cells (cor = − 0.386) (p < 0.05). Drug sensitivity analysis revealed that the IC50 values of 10 candidate compounds, including AZD6482, BX.798, and Bicalutamide, exhibited significant differences between the two groups (p < 0.05). RT-qPCR confirmed the overexpression of STMN1, UBE2T, CENPF, and FAM72C in ICCA tissues. Overall, this study highlights the significance of histone lactylation-associated prognostic genes and potential therapeutic targets in ICCA, providing insights into tumor microenvironment modulation and precision treatment approaches.