Single-cell and spatial transcriptomics reveal P4HA2-mediated radiotherapy resistance mechanisms in breast cancer.

ABSTRACT: Background: Radiotherapy resistance in breast cancer remains a major clinical challenge. The key molecular determinants and cellular populations driving this resistance are not fully understood. Methods: A radiotherapy resistance (RR) gene panel was identified from TCGA-BRCA and GSE120798 cohorts. Single-cell and spatial transcriptomics characterized RRhigh epithelial cells (RRhighepi). A prognostic model, named SuperPC and StepCox-based Radiotherapy Resistance model (SSRR), was built via machine learning and Mendelian randomization. Functional roles of Prolyl 4-Hydroxylase Subunit Alpha 2 (P4HA2) were validated in vitro. Results: The RR gene panel was upregulated in tumors and enriched for cell cycle pathways. RRhighepi cells exhibited elevated stemness,

SUBMITTER: Li H 

PROVIDER: S-EPMC12712805 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature