{"title":"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。","authors":"Md Shihabul Islam, Jesmin","doi":"10.1177/11772719241278176","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hypoxia, a condition where there is a lack of oxygen, is known to play a role in cancer progression.</p><p><strong>Objective: </strong>This study investigates the correlation between <i>HIF1A</i> gene-altered expression and hypoxia in Bangladeshi breast cancer (BC) cases and TCGA_BC datasets.</p><p><strong>Design: </strong>This case-control study compares BC cases to healthy controls to understand the relationship between gene changes and cancer.</p><p><strong>Method: </strong>This study used advanced analysis methods to examine the transcriptional landscape of BC, and quantitatively assessed its correlation using integrated multi-omics analysis.</p><p><strong>Results: </strong>In Bangladeshi BC cases, the T allele of <i>HIF1A</i> rs1154946 correlates notably (<i>P</i>-value < .001) with BC incidence. ELISA results confirmed a significant association (<i>P</i>-value < .005) between elevated <i>HIF1A</i> expression and BC-related hypoxia. Bioinformatics eQTL analysis validated the correlation between increased <i>HIF1A</i> expression and rs11549465 T allele (<i>P</i>-value < .01). Structural analyses suggested that rs11549465 (P582S) mutation may decrease protein stability (ΔΔG-value: -1.24 kcal/mole), potentially affecting <i>HIF1A</i> function. <i>HIF1A</i> enrichment analysis in BC underscores strong associations with oxygen levels, hypoxia, metabolic processes, apoptosis, and programed cell death (<i>P</i>-value < .001). Transcriptomic data demonstrated a robust correlation (<i>P</i>-value < .0001) between <i>HIF1A</i> expression and copy-number alterations, mutations, and abnormal methylation. Altered <i>HIF1A</i> expression showed strong negative correlations (<i>P</i>-value < .00001) with methylation and the expression of the ER (<i>ESR1</i>), in Whites. Survival analysis revealed marked differences in overall survival linked to high and low <i>HIF1A</i> expression (<i>P</i>-value < .00001). Furthermore, <i>HIF1A</i> expression significantly correlated (<i>P</i>-value < .000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment.</p><p><strong>Conclusion: </strong>Thus, the <i>HIF1A</i> gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241278176"},"PeriodicalIF":3.4000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418304/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring the Correlation Between Hypoxia, <i>HIF1A</i> Variants, and Breast Cancer in Different Ethnicities, and Bangladeshi Women: Through ELISA and Integrative Multi-Omics Analysis.\",\"authors\":\"Md Shihabul Islam, Jesmin\",\"doi\":\"10.1177/11772719241278176\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hypoxia, a condition where there is a lack of oxygen, is known to play a role in cancer progression.</p><p><strong>Objective: </strong>This study investigates the correlation between <i>HIF1A</i> gene-altered expression and hypoxia in Bangladeshi breast cancer (BC) cases and TCGA_BC datasets.</p><p><strong>Design: </strong>This case-control study compares BC cases to healthy controls to understand the relationship between gene changes and cancer.</p><p><strong>Method: </strong>This study used advanced analysis methods to examine the transcriptional landscape of BC, and quantitatively assessed its correlation using integrated multi-omics analysis.</p><p><strong>Results: </strong>In Bangladeshi BC cases, the T allele of <i>HIF1A</i> rs1154946 correlates notably (<i>P</i>-value < .001) with BC incidence. ELISA results confirmed a significant association (<i>P</i>-value < .005) between elevated <i>HIF1A</i> expression and BC-related hypoxia. Bioinformatics eQTL analysis validated the correlation between increased <i>HIF1A</i> expression and rs11549465 T allele (<i>P</i>-value < .01). Structural analyses suggested that rs11549465 (P582S) mutation may decrease protein stability (ΔΔG-value: -1.24 kcal/mole), potentially affecting <i>HIF1A</i> function. <i>HIF1A</i> enrichment analysis in BC underscores strong associations with oxygen levels, hypoxia, metabolic processes, apoptosis, and programed cell death (<i>P</i>-value < .001). Transcriptomic data demonstrated a robust correlation (<i>P</i>-value < .0001) between <i>HIF1A</i> expression and copy-number alterations, mutations, and abnormal methylation. Altered <i>HIF1A</i> expression showed strong negative correlations (<i>P</i>-value < .00001) with methylation and the expression of the ER (<i>ESR1</i>), in Whites. Survival analysis revealed marked differences in overall survival linked to high and low <i>HIF1A</i> expression (<i>P</i>-value < .00001). Furthermore, <i>HIF1A</i> expression significantly correlated (<i>P</i>-value < .000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment.</p><p><strong>Conclusion: </strong>Thus, the <i>HIF1A</i> gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation.</p>\",\"PeriodicalId\":47060,\"journal\":{\"name\":\"Biomarker Insights\",\"volume\":\"19 \",\"pages\":\"11772719241278176\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418304/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomarker Insights\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/11772719241278176\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomarker Insights","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/11772719241278176","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Exploring the Correlation Between Hypoxia, HIF1A Variants, and Breast Cancer in Different Ethnicities, and Bangladeshi Women: Through ELISA and Integrative Multi-Omics Analysis.
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.