Protein expression of BIRC5, TK1, and TOP2A in malignant peripheral nerve sheath tumours - A prognostic test after surgical resection

Matthias Kolberg, Maren Høland, Guro E. Lind, Trude H. Ågesen, Rolf I. Skotheim, Kirsten Sundby Hall, Nils Mandahl, Sigbjørn Smeland, Fredrik Mertens, Ben Davidson, Ragnhild A. Lothe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

No consensus treatment regime exists beyond surgery for malignant peripheral nerve sheath tumours (MPNST), and the purpose of the present study was to find new approaches to stratify patients with good and poor prognosis and to better guide therapeutic intervention for this aggressive soft tissue cancer. From a total of 67 MPNSTs from Scandinavian patients with and without neurofibromatosis type 1, 30 MPNSTs were investigated by genome-wide RNA expression profiling and 63 MPNSTs by immunohistochemical (IHC) analysis, and selected genes were submitted to analyses of disease-specific survival. The potential drug target genes survivin (BIRC5), thymidine kinase 1 (TK1), and topoisomerase 2-alpha (TOP2A), all encoded on chromosome arm 17q, were up-regulated in MPNST as compared to benign neurofibromas. Each of them was found to be independent prognostic markers on the gene expression level, as well as on the protein level. A prognostic profile was identified by combining the nuclear expression scores of the three proteins. For patients with completely resected tumours only 15% in the high risk group were alive after two years, as compared to 78% in the low risk group.In conclusion, we found a novel protein expression profile which identifies MPNST patients with inferior prognosis even after assumed curative surgery. The tested proteins are drug targets; therefore the expression profile may provide predictive information guiding the design of future clinical trials. Importantly, as the effect is seen on the protein level using IHC, the biomarker panel can be readily implemented in routine clinical testing.

Original languageEnglish (US)
Pages (from-to)1129-1139
Number of pages11
JournalMolecular oncology
Volume9
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Neurilemmoma
Proteins
Neurofibroma
Neurofibromatosis 1
Pharmaceutical Preparations
Genes
thymidine kinase 1
Neoplasms
Chromosomes
Biomarkers
Clinical Trials
Genome
RNA
Gene Expression
Survival
Therapeutics

Keywords

  • BIRC5
  • Immunohistochemistry
  • MPNST
  • Prognosis
  • Survivin
  • TK1
  • TOP2A

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

Cite this

Protein expression of BIRC5, TK1, and TOP2A in malignant peripheral nerve sheath tumours - A prognostic test after surgical resection. / Kolberg, Matthias; Høland, Maren; Lind, Guro E.; Ågesen, Trude H.; Skotheim, Rolf I.; Sundby Hall, Kirsten; Mandahl, Nils; Smeland, Sigbjørn; Mertens, Fredrik; Davidson, Ben; Lothe, Ragnhild A.

In: Molecular oncology, Vol. 9, No. 6, 01.06.2015, p. 1129-1139.

Research output: Contribution to journalArticle

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abstract = "No consensus treatment regime exists beyond surgery for malignant peripheral nerve sheath tumours (MPNST), and the purpose of the present study was to find new approaches to stratify patients with good and poor prognosis and to better guide therapeutic intervention for this aggressive soft tissue cancer. From a total of 67 MPNSTs from Scandinavian patients with and without neurofibromatosis type 1, 30 MPNSTs were investigated by genome-wide RNA expression profiling and 63 MPNSTs by immunohistochemical (IHC) analysis, and selected genes were submitted to analyses of disease-specific survival. The potential drug target genes survivin (BIRC5), thymidine kinase 1 (TK1), and topoisomerase 2-alpha (TOP2A), all encoded on chromosome arm 17q, were up-regulated in MPNST as compared to benign neurofibromas. Each of them was found to be independent prognostic markers on the gene expression level, as well as on the protein level. A prognostic profile was identified by combining the nuclear expression scores of the three proteins. For patients with completely resected tumours only 15{\%} in the high risk group were alive after two years, as compared to 78{\%} in the low risk group.In conclusion, we found a novel protein expression profile which identifies MPNST patients with inferior prognosis even after assumed curative surgery. The tested proteins are drug targets; therefore the expression profile may provide predictive information guiding the design of future clinical trials. Importantly, as the effect is seen on the protein level using IHC, the biomarker panel can be readily implemented in routine clinical testing.",
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