Circulating miRNA Expression Is Inversely Correlated with Tumor Tissue or Sentinel Lymph Nodes in Estrogen Receptor-Positive Early Breast Cancer Patients

Int J Mol Sci. 2023 Aug 27;24(17):13293. doi: 10.3390/ijms241713293.

Abstract

The deregulation of microRNAs (miRNAs) is associated with the various steps of the metastatic process. In addition, circulating miRNAs are remarkably stable in peripheral blood, making them ideal noninvasive biomarkers for disease diagnosis. Here, we performed a proof-of-principle study to determine whether tumor-tissue-derived miRNAs are traceable to plasma in ER-positive early breast cancer patients. We performed RNA-sequencing on 30 patients for whom plasma, sentinel lymph nodes (SLNs) and tumor tissue were available. We carried out differential expression, gene ontology and enrichment analyses. Our results show that circulating miRNAs are inversely expressed compared with tumor tissue or SLNs obtained from the same patients. Our differential expression analysis shows the overall downregulation of circulating miRNAs. However, the expression of miR-643a-3p and miR-223 was up-regulated in patients with positive SLNs. Furthermore, gene ontology analysis showed the significant enrichment of biological processes associated with the regulation of epithelial cell proliferation and transcriptional regulation commonly involved in the promotion of metastases. Our results suggest the potential role of several circulating miRNAs as surrogate markers of lymph node metastases in early breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant miRNAs and to validate our results in a larger cohort of patients.

Keywords: biomarkers; early breast cancer; metastasis; miRNAs; sentinel lymph node.

MeSH terms

  • Breast Neoplasms* / genetics
  • Circulating MicroRNA* / genetics
  • Female
  • Humans
  • MicroRNAs* / genetics
  • Receptors, Estrogen / genetics
  • Sentinel Lymph Node*

Substances

  • Receptors, Estrogen
  • MicroRNAs
  • Circulating MicroRNA

Grants and funding

This research was funded by grants PI13/00110 to D.E. and PI19/00362 to D.E. and A.B. from the Instituto de Salud Carlos III (ISCIII, Madrid, Spain) and co-funded by the European Regional Development Fund (Brussel, Belgium)grant CB16/12/00471 to A.B. from the Thematic Area for Cancer (CIBERONC, Madrid, Spain); grant 2021_SGR-00827 to A.B., D.E., C.A. and L.B. from the Catalonian Support to Research Groups (Barcelona, Catalunya, Spain).