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MicroRNA-Gene Networks Distinguish Hormone Receptor Status in HER2-Low Breast Cancer: An Integrative Transcriptomic

Eduarda Carvalho1,2, Andreia Brandão3, Fernando Schmitt1,2

  • 1PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.

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Summary
This summary is machine-generated.

This study reveals distinct microRNA (miRNA) and gene expression profiles in HER2-low breast cancer based on hormone receptor (HR) status. These findings identify potential biomarkers and therapeutic targets for understanding tumor diversity and guiding HR-directed treatments.

Keywords:
HER2-lowHR-negativeHR-positiveTCGA-BRCAbreast cancergeneshormone receptormicroRNAs

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Area of Science:

  • Molecular Oncology
  • Genomics and Transcriptomics
  • Biomarker Discovery

Background:

  • HER2-low breast cancer is heterogeneous, with hormone receptor (HR) status impacting prognosis and treatment.
  • MicroRNAs (miRNAs) are key regulators of gene expression and may influence HR heterogeneity.
  • Understanding the molecular mechanisms driving HR divergence in HER2-low tumors is crucial.

Purpose of the Study:

  • To identify deregulated miRNAs and gene networks distinguishing HER2-low/HR-positive from HER2-low/HR-negative breast cancer.
  • To elucidate the molecular mechanisms underlying transcriptomic divergence based on HR status.
  • To explore potential miRNA-based biomarkers and therapeutic targets for HER2-low breast cancer.

Main Methods:

  • Differential expression analysis of miRNAs and genes using Wilcoxon tests and DESeq2.
  • Survival analysis with Cox proportional hazards models.
  • Functional enrichment analysis (GO, KEGG, Reactome) and integrative miRNA-mRNA correlation/target prediction.

Main Results:

  • 165 miRNAs and 170 genes were significantly deregulated between HER2-low/HR-positive and HER2-low/HR-negative tumors.
  • miR-9-5p, miR-532-5p, and miR-576-5p were specifically associated with HR-negative status.
  • Distinct pathway enrichments (hormone-related in HR-positive; immune/inflammatory/proliferative in HR-negative) and two miRNA-mRNA axes (miR-576-5p/TGFBI, miR-9-5p/POU2F2) were identified.

Conclusions:

  • HER2-low breast cancer exhibits distinct miRNA and gene expression profiles correlating with HR status.
  • Specific miRNA-gene networks contribute to transcriptomic heterogeneity and may serve as biomarkers.
  • Findings support the development of HR-directed therapeutic strategies for HER2-low breast cancer.