Systemic Multi-Omics Analysis Reveals Amplified P4HA1 Gene Associated With Prognostic and Hypoxic Regulation in...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Breast cancer (BC) remains a leading cause of mortality in women globally, despite available therapies.
• Tumor hypoxia is a critical factor driving BC progression and treatment resistance.
• Understanding the molecular mechanisms of hypoxia in BC is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the role of hypoxia-induced genes in breast cancer progression.
• To identify potential biomarkers for early detection and therapeutic stratification in BC.

Main Methods:

• Analysis of two hypoxic-induced BC transcriptomic cohorts (GSE27813, GSE47533) from the GEO database.
• Identification and validation of the P4HA1 gene's expression and association with clinical subtypes.
• Assessment of P4HA1 copy number variations and their correlation with patient survival outcomes.
• Construction of a protein-protein interaction (PPI) network and functional enrichment analysis (GO, KEGG).

Main Results:

• The P4HA1 gene was significantly upregulated in hypoxic BC cells across various time intervals.
• P4HA1 expression strongly correlated with Luminal and triple-negative BC subclasses, Stage 1, lymph node N1, and the 40-80 age group.
• Elevated P4HA1 copy number at chromosomal band 10q22.1 was associated with poorer overall survival, relapse-free survival, and distant metastases-free survival.
• PPI network analysis revealed enrichment in cellular metabolic processes and hedgehog pathways.

Conclusions:

• The P4HA1 gene is a key player in hypoxic-mediated carcinogenesis in breast cancer.
• P4HA1 serves as a potential prognostic biomarker for BC patient survival.
• Findings support P4HA1's utility in early BC detection and therapeutic stratification.