Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

Research output: Contribution to journalArticle

Abstract

Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.

Details

Authors
  • Ulrik Ralfkiaer
  • Peter H Hagedorn
  • Nannie Bangsgaard
  • Marianne B Løvendorf
  • Charlotte B Ahler
  • Lars Svensson
  • Katharina L Kopp
  • Marie T Vennegaard
  • Britt Lauenborg
  • John R Zibert
  • Thorbjørn Krejsgaard
  • Charlotte M Bonefeld
  • Lise M Gjerdrum
  • Tord Labuda
  • Anne-Merete Mathiesen
  • Kirsten Grønbæk
  • Mariusz A. Wasik
  • Malgorzata Sokolowska-Wojdylo
  • Catherine Queille-Roussel
  • Robert Gniadecki
  • Elisabeth Ralfkiaer
  • Carsten Geisler
  • Thomas Litman
  • Anders Woetmann
  • Christian Glue
  • Mads A Røpke
  • Lone Skov
  • Niels Odum
External organisations
  • University of Copenhagen
Research areas and keywords

Keywords

  • Animals, Cells, Cultured, Female, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Humans, Lymphoma, T-Cell, Cutaneous, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, MicroRNAs, Microarray Analysis, Prognosis, Psoriasis, Transplantation, Heterologous, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Studies
Original languageEnglish
Pages (from-to)5891-900
Number of pages10
JournalBlood
Volume118
Issue number22
StatePublished - 2011 Nov 24
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes