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

Ralfkiaer, Ulrik; Hagedorn, Peter H; Bangsgaard, Nannie; Løvendorf, Marianne B; Ahler, Charlotte B; Svensson, Lars; Kopp, Katharina L; Vennegaard, Marie T; Lauenborg, Britt and Zibert, John R, et al. (2011) In Blood 118(22). p.900-5891
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... (More)

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.

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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
in
Blood
volume
118
issue
22
pages
10 pages
publisher
American Society of Hematology
external identifiers
  • scopus:80155124637
ISSN
1528-0020
DOI
10.1182/blood-2011-06-358382
language
English
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no
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ff272f59-e1d5-42b5-ab09-03aeb6b42436
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2017-09-01 14:30:21
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2017-11-12 04:34:53
@article{ff272f59-e1d5-42b5-ab09-03aeb6b42436,
  abstract     = {<p>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 &gt; 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.</p>},
  author       = {Ralfkiaer, Ulrik and Hagedorn, Peter H and Bangsgaard, Nannie and Løvendorf, Marianne B and Ahler, Charlotte B and Svensson, Lars and Kopp, Katharina L and Vennegaard, Marie T and Lauenborg, Britt and Zibert, John R and Krejsgaard, Thorbjørn and Bonefeld, Charlotte M and Søkilde, Rolf and Gjerdrum, Lise M and Labuda, Tord and Mathiesen, Anne-Merete and Grønbæk, Kirsten and Wasik, Mariusz A. and Sokolowska-Wojdylo, Malgorzata and Queille-Roussel, Catherine and Gniadecki, Robert and Ralfkiaer, Elisabeth and Geisler, Carsten and Litman, Thomas and Woetmann, Anders and Glue, Christian and Røpke, Mads A and Skov, Lone and Odum, Niels},
  issn         = {1528-0020},
  keyword      = {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},
  language     = {eng},
  month        = {11},
  number       = {22},
  pages        = {900--5891},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)},
  url          = {http://dx.doi.org/10.1182/blood-2011-06-358382},
  volume       = {118},
  year         = {2011},
}