Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin

Trent R. Hummel, Walter J. Jessen, Shyra J. Miller, Lan Kluwe, Victor F. Mautner, Margaret R. Wallace, Conxi Lázaro, Grier P. Page, Paul F Worley, Bruce J. Aronow, Elizabeth K. Schorry, Nancy Ratner

Research output: Contribution to journalArticle

Abstract

Purpose: Plexiform neurofibromas (pNF) are Schwann cell tumors found in a third of individuals with neurofibromatosis type 1 (NF1). pNF can undergo transformation tomalignant peripheral nerve sheath tumors (MPNST). There are no identified serum biomarkers of pNF tumor burden or transformation toMPNST. Serum biomarkers would be useful to verify NF1 diagnosis, monitor tumor burden, and/or detect transformation. Experimental Design: We used microarray gene expression analysis to define 92 genes that encode putative secreted proteins in neurofibroma Schwann cells, neurofibromas, and MPNST. We validated differential expression by quantitative reverse transcription-PCR, Western blotting, and ELISA assays in cell conditioned medium and control and NF1 patient sera. Results: Of 13 candidate genes evaluated, only adrenomedullin (ADM) was confirmed as differentially expressed and elevated in serum of NF1 patients. ADM protein concentrati on was further elevated in serum of a small sampling of NF1 patients with MPNST. MPNST cell conditioned medium, containing ADM and hepatocyte growth factor, stimulated MPNST migration and endothelial cell proliferation. Conclusions: Thus, microarray analysis identifies potential serum biomarkers for disease, and ADM is a serum biomarker of NF1. ADM serum levels do not seem to correlate with the presence of pNFs but may be a biomarker of transformation to MPNST.

Original languageEnglish (US)
Pages (from-to)5048-5057
Number of pages10
JournalClinical Cancer Research
Volume16
Issue number20
DOIs
StatePublished - Oct 15 2010

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Adrenomedullin
Neurofibromatosis 1
Neurilemmoma
Biomarkers
Gene Expression
Plexiform Neurofibroma
Serum
Neurofibroma
Schwann Cells
Conditioned Culture Medium
Tumor Burden
Nerve Sheath Neoplasms
Hepatocyte Growth Factor
Microarray Analysis
Genes
Reverse Transcription
Proteins
Research Design
Endothelial Cells
Western Blotting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hummel, T. R., Jessen, W. J., Miller, S. J., Kluwe, L., Mautner, V. F., Wallace, M. R., ... Ratner, N. (2010). Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. Clinical Cancer Research, 16(20), 5048-5057. https://doi.org/10.1158/1078-0432.CCR-10-0613

Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. / Hummel, Trent R.; Jessen, Walter J.; Miller, Shyra J.; Kluwe, Lan; Mautner, Victor F.; Wallace, Margaret R.; Lázaro, Conxi; Page, Grier P.; Worley, Paul F; Aronow, Bruce J.; Schorry, Elizabeth K.; Ratner, Nancy.

In: Clinical Cancer Research, Vol. 16, No. 20, 15.10.2010, p. 5048-5057.

Research output: Contribution to journalArticle

Hummel, TR, Jessen, WJ, Miller, SJ, Kluwe, L, Mautner, VF, Wallace, MR, Lázaro, C, Page, GP, Worley, PF, Aronow, BJ, Schorry, EK & Ratner, N 2010, 'Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin', Clinical Cancer Research, vol. 16, no. 20, pp. 5048-5057. https://doi.org/10.1158/1078-0432.CCR-10-0613
Hummel, Trent R. ; Jessen, Walter J. ; Miller, Shyra J. ; Kluwe, Lan ; Mautner, Victor F. ; Wallace, Margaret R. ; Lázaro, Conxi ; Page, Grier P. ; Worley, Paul F ; Aronow, Bruce J. ; Schorry, Elizabeth K. ; Ratner, Nancy. / Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 20. pp. 5048-5057.
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