Exploring the Role of HNRNPA3 in Breast Cancer Progression, Immune Microenvironment, and Therapeutic Sensitivity: A...

Breast invasive carcinoma (BRCA) remains a leading cause of female cancer mortality, necessitating novel biomarkers and therapeutic targets. Heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) emerges as a potential regulator in tumor progression and immune modulation, yet its comprehensive role in BRCA remains uncharacterized.

We conducted an integrated multiomics analysis of HNRNPA3 in BRCA using data from TCGA, GEO datasets, single-cell RNA sequencing, and spatial transcriptomics. Bioinformatics approaches included differential expression analysis, survival analysis, functional enrichment, immune microenvironment characterization, and drug sensitivity prediction.

HNRNPA3 was significantly upregulated in BRCA tissues and correlated with advanced tumor grade, metastasis, and poor prognosis across multiple cohorts. Functional enrichment revealed HNRNPA3's involvement in cell cycle regulation and immune-related pathways. Immune profiling demonstrated that high HNRNPA3 expression was associated with altered immune cell distribution, particularly CD4+ T cells, and reduced immunotherapy response. Spatial transcriptomics confirmed predominant HNRNPA3 expression in malignant regions. Drug sensitivity analysis identified potential therapeutic agents (CD-437 and talazoparib) targeting HNRNPA3-associated pathways.

HNRNPA3 functions as a critical oncogenic regulator in BRCA by promoting tumor progression through cell cycle dysregulation and immune microenvironment remodeling. Its strong association with therapy resistance positions HNRNPA3 as both a prognostic biomarker and promising therapeutic target for breast cancer intervention strategies.