Somatostatin Analogs Treated Small Intestinal Neuroendocrine Tumor Patients Circulating MicroRNAs

PLoS One. 2015 May 5;10(5):e0125553. doi: 10.1371/journal.pone.0125553. eCollection 2015.

Abstract

We previously detected and investigated nine altered microRNAs in small intestinal neuroendocrine tumor (SI-NET) tissues at different stages of disease. The aims of this study are to: 1) analyze whether SI-NET tissue microRNAs can be also detected in patient serum samples, 2) investigate a potential somatostatin analogs (SSAs) role on microRNA levels regulation in SSA-treated patient samples and 3) elucidate whether the serum microRNA levels in samples collected in different hospitals are predictable and steady. Our results show that tissue microRNAs are detectable in patient serum samples, and miR-96, -182, -183, -196a and -200a levels are lower in SI-NET untreated patients than in SSA-treated patients at all different stages. Conversely, miR-31, -129-5p, -133a and -215 levels do not show any difference in untreated SI-NET patients and SSA-treated patients at all different stages. Our findings also show that miR-200a exhibits an atypical behavior with high levels in both untreated and SSA-treated patients at liver metastasis stage, and unequivocally never at the earlier stages. Serum samples collected in two hospitals keep alike microRNA level pattern, elucidating that the results are not dependent on samples handling. In conclusion, SI-NET tissue microRNAs are always detectable in untreated and SSA-treated patient serum samples, SSAs play an unknown role in eliciting SSA-treated patients' microRNA levels higher than in untreated patients, and this study enlightens that miR-200a might be involved in the liver metastasis during SI-NET progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intestinal Neoplasms / blood
  • Intestinal Neoplasms / drug therapy*
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / pathology
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neuroendocrine Tumors / blood
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / pathology
  • Real-Time Polymerase Chain Reaction
  • Somatostatin / analogs & derivatives
  • Somatostatin / therapeutic use*

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Somatostatin

Grants and funding

This work was supported by funding from the Lions Cancer Research, and Erik, Karin and Gösta Selander Foundation. The funders had no role in study design, data collection analysis and interpretation of data, decision to publish or preparation of the manuscript.