An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer
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* Corresponding authors: Juan Ángel Fresno Vara jafresno@gmail.com - Enrique Espinosa eespinosa00@terra.es
- Equal contributors
1 Unidad de Investigación, Instituto de Investigación Sanitaria IdIPAZ, Hospital Universitario La Paz (Paseo de la Castellana, 261), Madrid (28046), Spain
2 Service of Oncology, IdIPAZ, Hospital Universitario La Paz (Paseo de la Castellana, 261), Madrid (28046), Spain
3 Service of Pathology, IdIPAZ, Hospital Universitario La Paz (Paseo de la Castellana, 261), Madrid (28046), Spain
4 Service of Statistics, IdIPAZ, Hospital Universitario La Paz (Paseo de la Castellana, 261), Madrid (28046), Spain
5 Chair of Oncology & Palliative care, Facultad de Medicina, Universidad Autónoma de Madrid (Arzobispo Morcillo n° 2 y 4), Madrid (28029), Spain
BMC Cancer 2010, 10:336 doi:10.1186/1471-2407-10-336
Published: 28 June 2010Abstract
Background
Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.
Methods
We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models.
Results
An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database.
Conclusions
This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.