title: The association of blood angioregulatory microRNA levels with circulating endothelial cells and angiogenic proteins in patients receiving dacarbazine and interferon.
abstract: BACKGROUND
  Blood biomarkers are needed to monitor anti-angiogenic treatments for cancer. The association of blood levels of microRNAs (miRs) implicated in angiogenesis with circulating endothelial cells (CEC) and with angiogenic proteins was examined in patients administered drugs with anti-angiogenic activity.
  
  
  METHODS
  Blood was collected from patients with uveal melanoma enrolled on an adjuvant therapy trial in which they were treated sequentially with dacarbazine and interferon-alfa-2b. Plasma levels of nine angioregulatory miRs, miR-16, 20a, 106a, 125b, 126, 146a, 155, 199a, and 221, were determined by quantitative real time polymerase chain reaction; CEC, by semi-automated immunomagnetic; and plasma angiogenic proteins, by enzyme linked immunosorbent assays.
  
  
  RESULTS
  Levels of miR-199a were positively correlated and miR-106a negatively correlated with CEC pre-therapy. Decreases in miR-126 and miR-199a and increases in miR-16 and miR-106a were observed after interferon-alfa-2b, but not after dacarbazine. CEC also increased after treatment with interferon but not after treatment with dacarbazine. Levels of miRs did not correlate with levels of vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8. Angiogenic proteins also did not change significantly with treatment.
  
  
  CONCLUSIONS
  Blood levels of specific angioregulatory miRs are associated with CEC, and changes in specific angioregulatory miRs parallel increases in CEC after treatment with interferon-alfa-2b. Blood levels of specific angioregulatory miRs are not associated with levels of angiogenic proteins. miRs warrant further evaluation as blood biomarkers of angiogenesis.
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. triozzp@ccf.org
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
authors.forename: Susan
authors.initials: S
authors.lastname: Achberger
authors.forename: Wayne
authors.initials: W
authors.lastname: Aldrich
authors.forename: Arun D
authors.initials: AD
authors.lastname: Singh
authors.forename: Ronald
authors.initials: R
authors.lastname: Grane
authors.forename: Ernest C
authors.initials: EC
authors.lastname: Borden
mesh_terms: D042501:Angiogenic Proteins / Q000097:blood*; D002465:Cell Movement / Q000187:drug effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008545:Melanoma / Q000097:blood / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D035683:MicroRNAs / Q000097:blood*; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014604:Uveal Neoplasms / Q000097:blood / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D042501:Angiogenic Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D035683:MicroRNAs; D011994:Recombinant Proteins; D003606:Dacarbazine