Work

Integrated analysis reveals survival-related genes promoting cholangiocarcinoma progression via G2/M cell cycle, with validation of cyclin B1 in tumor proliferation

Year: 2025

Type: article

Abstract: Cholangiocarcinoma (CCA) progression involves dysregulated cell cycle control, but core regulatory networks and their roles in tumor heterogeneity remain elusive. We integrated bulk transcriptomics (TCGA-CHOL and GEO cohorts) and single-cell RNA-seq (GSE138709) to identify survival-related genes (SRGs) driving CCA. Through limma, WGCNA, and PPI analysis, we identified seven SRGs (CDK1, ASPM, CCNB1, KIF2C, TOP2A, BUB1, DLGAP5) enriched in G2/M-phase pathways. Single-cell analysis revealed specific SRG upregulation in malignant epithelial subpopulations (PHGR1-Epi/UBE2C-Epi), with pseudotime trajectories demonstrating dynamically increased SRG expression during dedifferentiation. Functional validation confirmed CCNB1 as a core regulator: siRNA knockdown in HuCCT1/RBE cells significantly suppressed proliferation and clonogenicity. This study is the first to define a G2/M-phase gene module promoting CCA progression and map its single-cell dynamics, highlighting CCNB1 as a therapeutic target. Our results reveal SRGs as a coordinated oncogenic network underlying tumor aggressiveness, providing mechanistic insights for future SRG-targeted therapies.

Source: Scientific Reports

DOI: 10.1038/s41598-025-25299-4