Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity.
Sarcomas are heterogeneous and aggressive mesenchymal tumors. Histological grading has so far been the best predictor for metastasis-free survival, but it has several limitations, such as moderate reproducibility and poor prognostic value for some histological types. To improve patient grading, we performed genomic and expression profiling in a training set of 183 sarcomas and established a prognostic gene expression signature, complexity index in sarcomas (CINSARC), composed of 67 genes related to mitosis and chromosome management. In a multivariate analysis, CINSARC predicts metastasis outcome in the training set and in an independent 127 sarcomas validation set. It is superior to the Fédération Francaise des Centres de Lutte Contre le Cancer grading system in determining metastatic outcome for sarcoma patients. Furthermore, it also predicts outcome for gastrointestinal stromal tumors (GISTs), breast carcinomas and lymphomas. Application of the signature will permit more selective use of adjuvant therapies for people with sarcomas, leading to decreased iatrogenic morbidity and improved outcomes for such individuals.
Chibon
Frédéric
F
Département de Pathologie, Institut Bergonié, Bordeaux, France. chibon@bergonie.org
Lagarde
Pauline
P
Salas
Sébastien
S
Pérot
Gaëlle
G
Brouste
Véronique
V
Tirode
Franck
F
Lucchesi
Carlo
C
de Reynies
Aurélien
A
Kauffmann
Audrey
A
Bui
Binh
B
Terrier
Philippe
P
Bonvalot
Sylvie
S
Le Cesne
Axel
A
Vince-Ranchère
Dominique
D
Blay
Jean-Yves
JY
Collin
Françoise
F
Guillou
Louis
L
Leroux
Agnès
A
Coindre
Jean-Michel
JM
Aurias
Alain
A
D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D005544:Forecasting; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology*; D016896:Treatment Outcome