Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Picture of Patrik Edén

Patrik Edén

Senior Lecturer

Picture of Patrik Edén

Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential.

Author

  • Princy Francis
  • Heidi Maria Namlos
  • Christoph Müller
  • Patrik Edén
  • Josefin Fernebro
  • Jeanne-Marie Berner
  • Bodil Bjerkehagen
  • Måns Åkerman
  • Pär-Ola Bendahl
  • Anna Isinger Ekstrand
  • Anders Rydholm
  • Ola Myklebost
  • Mef Nilbert

Summary, in English

Background



Soft tissue sarcoma (STS) diagnosis is challenging because of a multitude of histopathological subtypes, different genetic characteristics, and frequent intratumoral pleomorphism. One-third of STS metastasize and current risk-stratification is suboptimal, therefore, novel diagnostic and prognostic markers would be clinically valuable. We assessed the diagnostic and prognostic value of array-based gene expression profiles using 27 k cDNA microarrays in 177, mainly high-grade, STS of 13 histopathological subtypes.

Results



Unsupervised analysis resulted in two major clusters – one mainly containing STS characterized by type-specific genetic alterations and the other with a predominance of genetically complex and pleomorphic STS. Synovial sarcomas, myxoid/round-cell liposarcomas, and gastrointestinal stromal tumors clustered tightly within the former cluster and discriminatory signatures for these were characterized by developmental genes from the EGFR, FGFR, Wnt, Notch, Hedgehog, RAR and KIT signaling pathways. The more pleomorphic STS subtypes, e.g. leiomyosarcoma, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma, were part of the latter cluster and were characterized by relatively heterogeneous profiles, although subclusters herein were identified. A prognostic signature partly characterized by hypoxia-related genes was identified among 89 genetically complex pleomorphic primary STS and could, in a multivariate analysis including established prognostic markers, independently predict the risk of metastasis with a hazard ratio of 2.2 (P = 0.04).

Conclusion



Diagnostic gene expression profiles linking signaling pathways to the different STS subtypes were demonstrated and a hypoxia-induced metastatic profile was identified in the pleomorphic, high-grade STS. These findings verify diagnostic utility and application of expression data for improved selection of high-risk STS patients.

Department/s

  • Breastcancer-genetics
  • Computational Biology and Biological Physics
  • Tumor microenvironment
  • Department of Immunotechnology
  • Orthopaedics (Lund)

Publishing year

2007

Language

English

Publication/Series

BMC Genomics

Volume

8

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Genetics

Status

Published

ISBN/ISSN/Other

  • ISSN: 1471-2164