Transcription Factor Networks Drive Tumor Progression and Immune Microenvironment Remodeling in Hepatocellular Carcinoma.

ABSTRACT: (1) Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality and is characterized by pronounced inter- and intra-tumoral heterogeneity and therapy resistance. We aimed to define core transcriptional circuits that drive HCC malignancy and to delineate how these programs shape the tumor microenvironment (TME). (2) Methods: We integrated single-cell, spatial, and bulk transcriptomic datasets from public cohorts. (3) Results: We identified nine tumor-restricted transcription factors (TFs)-HTATIP2, HES6, ILF2, E2F1, MYBL2, DDIT3, FOXM1, HMGA1, and ETV4-whose expression and regulon activity associated with malignant phenotypes and poor survival. These TFs organize a progression axis from an early proliferative state (cluster C4) toward an invasive, metabolically adapt

SUBMITTER: Lee SH 

PROVIDER: S-EPMC12691271 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature