Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential.
Francis, Princy LU ; Namlos, Heidi Maria ; Müller, Christoph ; Edén, Patrik LU ; Fernebro, Josefin LU ; Berner, Jeanne-Marie ; Bjerkehagen, Bodil ; Åkerman, Måns LU ; Bendahl, Pär-Ola LU and Isinger Ekstrand, Anna LU
, et al.
(2007)
In BMC Genomics
8.
- Abstract
- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/166551
- author
- Francis, Princy
LU
; Namlos, Heidi Maria
; Müller, Christoph
; Edén, Patrik
LU
; Fernebro, Josefin
LU
; Berner, Jeanne-Marie
; Bjerkehagen, Bodil
; Åkerman, Måns
LU
; Bendahl, Pär-Ola
LU
and Isinger Ekstrand, Anna
LU
, et al. (More)
- Francis, Princy
LU
; Namlos, Heidi Maria
; Müller, Christoph
; Edén, Patrik
LU
; Fernebro, Josefin
LU
; Berner, Jeanne-Marie
; Bjerkehagen, Bodil
; Åkerman, Måns
LU
; Bendahl, Pär-Ola
LU
; Isinger Ekstrand, Anna
LU
; Rydholm, Anders
LU
; Myklebost, Ola
and Nilbert, Mef
LU
(Less)
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMC Genomics
- volume
- 8
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000245454400001
- scopus:34047129837
- ISSN
- 1471-2164
- DOI
- 10.1186/1471-2164-8-73
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Oncology, MV (013035000), Department of Orthopaedics (Lund) (013028000), Computational biology and biological physics (000006113), Pathology, (Lund) (013030000), Department of Immunotechnology (011029300)
- id
- be8584f3-367c-4203-a6a6-e4fbe99206a8 (old id 166551)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17359542&dopt=Abstract
- date added to LUP
- 2016-04-01 16:39:26
- date last changed
- 2022-12-12 20:23:20
@article{be8584f3-367c-4203-a6a6-e4fbe99206a8,
abstract = {{Background<br/><br>
<br/><br>
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.<br/><br>
Results<br/><br>
<br/><br>
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).<br/><br>
Conclusion<br/><br>
<br/><br>
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.}},
author = {{Francis, Princy and Namlos, Heidi Maria and Müller, Christoph and Edén, Patrik and Fernebro, Josefin and Berner, Jeanne-Marie and Bjerkehagen, Bodil and Åkerman, Måns and Bendahl, Pär-Ola and Isinger Ekstrand, Anna and Rydholm, Anders and Myklebost, Ola and Nilbert, Mef}},
issn = {{1471-2164}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Genomics}},
title = {{Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential.}},
url = {{https://lup.lub.lu.se/search/files/4737400/625898.pdf}},
doi = {{10.1186/1471-2164-8-73}},
volume = {{8}},
year = {{2007}},
}