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Molecular Cancer Research
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Research Article

Discovery-based Protein Expression Profiling Identifies Distinct Subgroups and Pathways in Leiomyosarcomas

Ufuk Kirik, Karin Hansson, Morten Krogh, Mats Jonsson, Mef Nilbert, Peter James and Ana Carneiro
Ufuk Kirik
1Immunotechnology, Lund University
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Karin Hansson
1Immunotechnology, Lund University
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Morten Krogh
2Amber Biosciences AB
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Mats Jonsson
2Amber Biosciences AB
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Mef Nilbert
3Department of Oncology, Institute of Clinical Sciences, Lund University
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Peter James
1Immunotechnology, Lund University
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  • For correspondence: peter.james@immun.lth.se
Ana Carneiro
4Clinical Research Centre, Hvidovre Hospital, Copenhagen University
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DOI: 10.1158/1541-7786.MCR-14-0072
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Abstract

Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathological and molecular classification of these tumors has been a significant challenge. This study examines the protein expression of a large number of human softtissue sarcomas, including subtype heterogeneity, using 2D-gel proteomics. In addition, detailed proteome profiles of a subset of pleomorphic STS specimens using an in-depth mass-spectrometry approach and identified subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biological nodes like apoptosis, cytoskeleton remodeling and telomere regulation are differentially regulated among these subgroups. Finally, investigating the Kirik et al. Protein profiling of leiomyosarcoma Page 2 of 24 similarities between protein expression of leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar protein expression profiles for these tumors, in comparison to pleomorphic leiomyosarcomas. Implications: These results suggest that UPS tumors share a similar lineage as leiomyosarcomas, and are likely to originate from different stages of differentiation from mesenchymal stem cells to smooth muscle cells.

  • Received February 7, 2014.
  • Revision received July 2, 2014.
  • Accepted July 6, 2014.
  • Copyright © 2014, American Association for Cancer Research.
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This OnlineFirst version was published on July 28, 2014
doi: 10.1158/1541-7786.MCR-14-0072

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Discovery-based Protein Expression Profiling Identifies Distinct Subgroups and Pathways in Leiomyosarcomas
Ufuk Kirik, Karin Hansson, Morten Krogh, Mats Jonsson, Mef Nilbert, Peter James and Ana Carneiro
Mol Cancer Res July 28 2014 DOI: 10.1158/1541-7786.MCR-14-0072

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Discovery-based Protein Expression Profiling Identifies Distinct Subgroups and Pathways in Leiomyosarcomas
Ufuk Kirik, Karin Hansson, Morten Krogh, Mats Jonsson, Mef Nilbert, Peter James and Ana Carneiro
Mol Cancer Res July 28 2014 DOI: 10.1158/1541-7786.MCR-14-0072
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Molecular Cancer Research
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