Serum levels of miR-223 but not miR-21 are decreased in patients with neuroendocrine tumors

PLoS One. 2020 Dec 31;15(12):e0244504. doi: 10.1371/journal.pone.0244504. eCollection 2020.


Background and aims: MicroRNAs (miRNAs) are profoundly involved into the pathophysiology of manifold cancers. Recent data suggested a pivotal role of miRNAs as biomarkers in different biological processes including carcinogenesis. However, their role in neuroendocrine tumors (NETs) is only poorly understood.

Methods: We determined circulating levels of miR-21 and miR-223 in 45 samples from patients with NET treated between 2010 and 2019 at our department and compared them to healthy controls. Results were correlated with clinical records.

Results: In the total cohort of Patients with NET, miR-223 presented significantly lower levels compared to healthy control samples. In contrast, levels of miR-21 indicated no significant changes between the two groups. Interestingly, despite being significantly downregulated in all NET patients, concentrations of miR-223 were independent of clinical or histopathological factors such as proliferation activity according to Ki-67 index, tumor grading, TNM stage, somatostatin receptor expression, presence of functional/ non-functional disease or tumor relapse. Moreover, in contrast to data from recent publications analyzing other tumor entities, levels of miR-223 serum levels did not reflect prognosis of patients with NET.

Conclusion: Lower concentrations of circulating miR-223 rather reflect the presence of NET itself than certain tumor characteristics. The value of miR-223 as a biomarker in NET might be limited to diagnostic, but not prognostic purposes.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Healthy Volunteers
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Neuroendocrine Tumors / blood
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / therapy
  • Prognosis
  • Young Adult


  • Biomarkers, Tumor
  • MIRN21 microRNA, human
  • MIRN223 microRNA, human
  • MicroRNAs

Grant support

The authors received no specific funding for this work.