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Purpose <p>Biogenic amines (BAs) are known to influence tumorigenesis, yet their precise role in breast cancer remains unclear. This study aimed to investigate the expression patterns of BA-related genes, proteins, and their regulatory miRNAs across different breast cancer subtypes to identify potential biomarkers and therapeutic targets.</p> Methods <p>A cohort of 501 breast cancer patients was classified into luminal A (<i>n</i> = 130), luminal B HER2− (<i>n</i> = 100), luminal B HER2+ (<i>n</i> = 96), non-luminal HER2+ (<i>n</i> = 36), and triple-negative breast cancer (TNBC; <i>n</i> = 43). Gene expression was assessed via microarray analysis and validated using RT-qPCR. Protein levels were quantified using ELISA, while miRNA profiling was conducted to identify post-transcriptional regulatory interactions. Statistical significance was determined using ANOVA and Tukey’s post-hoc test (<i>p</i> &lt; 0.05).</p> Results <p>Histamine-related genes (HRH1-HRH4) were upregulated across all subtypes, with HRH2 and HRH4 most elevated in TNBC (FC = 7.18, <i>p</i> &lt; 0.01). DRD2 showed widespread upregulation (FC = 15.98, <i>p</i> &lt; 0.001), whereas DRD5 was markedly downregulated, especially in non-luminal HER2+ tumors (FC =  − 13.01, <i>p</i> &lt; 0.01). miRNA analysis revealed downregulation of hsa-miR-30b-3p and hsa-miR-372-5p in TNBC and HER2+ subtypes, correlating with HRH2 and HRH4 overexpression (<i>p</i> &lt; 0.05). EGR1 and ICAM1 exhibited strong subtype-specific expression, with ICAM1 significantly upregulated in TNBC (FC = 25.76, <i>p</i> &lt; 0.001).</p> Conclusion <p>Subtype-specific dysregulation of BA-related genes and miRNAs suggests their involvement in tumor progression, immune modulation, and metabolic regulation. The findings highlight potential therapeutic targets, particularly in TNBC and HER2+ subtypes.</p>

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Subtype-specific dysregulation of biogenic amine-related genes and miRNAs in breast cancer: identification of DRD2, HRH2, and HRH4 as potential therapeutic targets in TNBC and HER2+ subtypes

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  • 发表日期：

    2025年5月27日

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  • Agata Sirek,
  • Tomasz Sirek,
  • Robert Nowakowski,
  • Przemysław Borawski,
  • Piotr Ossowski,
  • Elżbieta Mitka-Krysiak,
  • Nikola Zmarzły,
  • Kacper Boroń,
  • Michał Chalcarz,
  • Bernadeta Kuraszewska,
  • Mariola Szulik,
  • Dariusz Boroń,
  • Beniamin Oskar Grabarek

摘要

Purpose

Biogenic amines (BAs) are known to influence tumorigenesis, yet their precise role in breast cancer remains unclear. This study aimed to investigate the expression patterns of BA-related genes, proteins, and their regulatory miRNAs across different breast cancer subtypes to identify potential biomarkers and therapeutic targets.

Methods

A cohort of 501 breast cancer patients was classified into luminal A (n = 130), luminal B HER2− (n = 100), luminal B HER2+ (n = 96), non-luminal HER2+ (n = 36), and triple-negative breast cancer (TNBC; n = 43). Gene expression was assessed via microarray analysis and validated using RT-qPCR. Protein levels were quantified using ELISA, while miRNA profiling was conducted to identify post-transcriptional regulatory interactions. Statistical significance was determined using ANOVA and Tukey’s post-hoc test (p < 0.05).

Results

Histamine-related genes (HRH1-HRH4) were upregulated across all subtypes, with HRH2 and HRH4 most elevated in TNBC (FC = 7.18, p < 0.01). DRD2 showed widespread upregulation (FC = 15.98, p < 0.001), whereas DRD5 was markedly downregulated, especially in non-luminal HER2+ tumors (FC =  − 13.01, p < 0.01). miRNA analysis revealed downregulation of hsa-miR-30b-3p and hsa-miR-372-5p in TNBC and HER2+ subtypes, correlating with HRH2 and HRH4 overexpression (p < 0.05). EGR1 and ICAM1 exhibited strong subtype-specific expression, with ICAM1 significantly upregulated in TNBC (FC = 25.76, p < 0.001).

Conclusion

Subtype-specific dysregulation of BA-related genes and miRNAs suggests their involvement in tumor progression, immune modulation, and metabolic regulation. The findings highlight potential therapeutic targets, particularly in TNBC and HER2+ subtypes.