Exploring the Correlation Between Hypoxia, HIF1A Variants, and Breast Cancer in Different Ethnicities, and Bangladeshi Women: Through ELISA and Integrative Multi-Omics Analysis.

IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Biomarker Insights Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI:10.1177/11772719241278176
Md Shihabul Islam, Jesmin
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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.

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通过酶联免疫吸附试验和综合多组学分析探讨不同种族和孟加拉妇女缺氧、HIF1A 变异与乳腺癌之间的相关性:通过 ELISA 和综合多指标分析。
背景:缺氧是一种缺氧状态,已知在癌症进展过程中起作用:本研究调查了孟加拉国乳腺癌(BC)病例和 TCGA_BC 数据集中 HIF1A 基因表达改变与缺氧之间的相关性:这项病例对照研究将孟加拉乳腺癌病例与健康对照进行比较,以了解基因变化与癌症之间的关系:本研究采用先进的分析方法研究了孟加拉国乳腺癌的转录格局,并利用多组学综合分析方法对其相关性进行了定量评估:结果:在孟加拉国的BC病例中,HIF1A rs1154946的T等位基因与BC相关缺氧显著相关(P-value P-value HIF1A表达)。生物信息学 eQTL 分析验证了 HIF1A 表达增加与 rs11549465 T 等位基因的相关性(P-value HIF1A 功能)。对 BC 中 HIF1A 的富集分析表明,HIF1A 与氧水平、缺氧、代谢过程、细胞凋亡和程序性细胞死亡密切相关(P-value HIF1A 表达与拷贝数改变、突变和异常甲基化有关。在白人中,HIF1A表达的改变显示出强烈的负相关(P值ESR1)。生存分析表明,HIF1A 高表达和低表达在总生存率上存在明显差异(P-value HIF1A 表达显著相关(P-value 结论):因此,HIF1A 基因可作为乳腺癌进展、控制和跨种族生存的有前途的生物标记物,强调其在疾病发展和调节中的作用。
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来源期刊
Biomarker Insights
Biomarker Insights MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.00
自引率
0.00%
发文量
26
审稿时长
8 weeks
期刊介绍: An open access, peer reviewed electronic journal that covers all aspects of biomarker research and clinical applications.
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