Integrative Genomic and Transcriptomic Analysis Identifies BAX as a Prognostic Marker of Disease Progression in...

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Prostate cancer is a prevalent malignancy with variable outcomes following androgen deprivation therapy (ADT).
• Endoplasmic reticulum (ER) stress and the unfolded protein response are implicated in tumor adaptation and disease progression.

Purpose of the Study:

• To investigate the association between genetic variants in ER stress-related genes and survival outcomes in prostate cancer patients receiving ADT.
• To explore the biological mechanisms underlying these associations using gene expression and immune infiltration data.

Main Methods:

• Genetic association analysis of 89 single-nucleotide polymorphisms (SNPs) in 12 ER stress-related genes among 630 prostate cancer patients undergoing ADT.
• Kaplan-Meier survival analysis and Cox proportional hazards models for overall survival (OS) assessment.
• Integration of public databases for gene expression, clinical relevance, gene set enrichment, and tumor immune infiltration analysis.

Main Results:

• The BAX rs182509214 SNP showed the strongest association with OS, with the minor G allele linked to poorer survival.
• Elevated BAX expression in prostate tumors correlated with worse survival outcomes and was confirmed across public datasets.
• BAX alterations were associated with enrichment in ribosomal, oxidative phosphorylation, and proteasomal pathways, and negatively correlated with CD8+ T-cell infiltration.

Conclusions:

• The ER stress-related genetic variant BAX rs182509214 may influence survival in prostate cancer patients on ADT.
• BAX alterations are linked to disease progression, mitochondria-related metabolic pathways, and the tumor immune microenvironment.
• BAX warrants further investigation as a potential prognostic biomarker for prostate cancer treated with ADT.