Abstract
BACKGROUND: Hypoxia, a condition where there is a lack of oxygen, is known to play a role in cancer progression. OBJECTIVE: This study investigates the correlation between HIF1A gene-altered expression and hypoxia in Bangladeshi breast cancer (BC) cases and TCGA_BC datasets. DESIGN: This case-control study compares BC cases to healthy controls to understand the relationship between gene changes and cancer. METHOD: This study used advanced analysis methods to examine the transcriptional landscape of BC, and quantitatively assessed its correlation using integrated multi-omics analysis. RESULTS: In Bangladeshi BC cases, the T allele of HIF1A rs1154946 correlates notably (P-value < .001) with BC incidence. ELISA results confirmed a significant association (P-value < .005) between elevated HIF1A expression and BC-related hypoxia. Bioinformatics eQTL analysis validated the correlation between increased HIF1A expression and rs11549465 T allele (P-value < .01). Structural analyses suggested that rs11549465 (P582S) mutation may decrease protein stability (ΔΔG-value: -1.24 kcal/mole), potentially affecting HIF1A function. HIF1A enrichment analysis in BC underscores strong associations with oxygen levels, hypoxia, metabolic processes, apoptosis, and programed cell death (P-value < .001). Transcriptomic data demonstrated a robust correlation (P-value < .0001) between HIF1A expression and copy-number alterations, mutations, and abnormal methylation. Altered HIF1A expression showed strong negative correlations (P-value < .00001) with methylation and the expression of the ER (ESR1), in Whites. Survival analysis revealed marked differences in overall survival linked to high and low HIF1A expression (P-value < .00001). Furthermore, HIF1A expression significantly correlated (P-value < .000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment. CONCLUSION: Thus, the HIF1A gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation.