An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

Abstract

BackgroundGene 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.MethodsWe 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.ResultsAn 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.ConclusionsThis study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.

Testing an Aflatoxin B1 Gene Signature in Rat Archival Tissues

“…Use of random hexamers for reverse transcriptase reactions and primers for relatively short amplicons were important steps in using degraded RNA as a template for amplification in qPCR. 7, 48 qPCR has been used to obtain gene expression data from FFPE samples from different tissue types and organs, often with tumor specimens to improve prognostic accuracy in clinical care. 7, 12, 15, 49 For example, RNA from FFPE samples of 153 breast cancer patients were used to develop an 8-gene qPCR gene expression score of prognostic value that could be reasonably implemented in clinical settings without the need for fresh frozen RNA or more costly commercial signature arrays.…”

“…7, 48 qPCR has been used to obtain gene expression data from FFPE samples from different tissue types and organs, often with tumor specimens to improve prognostic accuracy in clinical care. 7, 12, 15, 49 For example, RNA from FFPE samples of 153 breast cancer patients were used to develop an 8-gene qPCR gene expression score of prognostic value that could be reasonably implemented in clinical settings without the need for fresh frozen RNA or more costly commercial signature arrays. 7 One recent study identified a 14 gene expression signature using qPCR with FFPE RNA from a 361 patient cohort to predict survival in nonsquamous, non-small-cell lung cancer.…”

RecurrenceOnline: an online analysis tool to determine breast cancer recurrence and hormone receptor status using microarray data

“…patients (3), LN? patients (4) and the predictive power of the recurrence-online computed recurrence score (5) already confirmed by the MAQC consortia [31]. However, the high data volume and data complexity in microarray experiments carry many potential sources of unwanted variation that could compromise the results if left uncontrolled.…”

The present and future of gene profiling in breast cancer

“…Some other signatures have been described but remain in the early phases of development [5][6][7][8]. From the clinical point of view, their value depends on the identification of a subgroup of patients with a very favorable outcome who do not require adjuvant chemotherapy.…”