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A prognostic gene expression profile that predicts circulating tumor cell presence in breast cancer patients.

Molloy TJ, Roepman P, Naume B, van't Veer LJ - PLoS ONE (2012)

Bottom Line: The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer.In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome.This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

ABSTRACT
The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into "good prognosis" or "poor prognosis" are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the "CTC profile" also provided prognostic information independent of the well-established and powerful '70-gene' prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays.

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Related in: MedlinePlus

Network analysis of CTC-profile genes indicted two main functional networks: a cellular survival/proliferation associated network (colored orange) and a cellular migration/angiogenesis related network (colored purple).CTC-profile genes are indicated by grey symbols.
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pone-0032426-g004: Network analysis of CTC-profile genes indicted two main functional networks: a cellular survival/proliferation associated network (colored orange) and a cellular migration/angiogenesis related network (colored purple).CTC-profile genes are indicated by grey symbols.

Mentions: Functional annotation and gene network analysis demonstrated two main networks comprising 29 of the 34 CTC-profile genes (Figure 4). One network (16 genes) was enriched for genes associated with cellular survival and proliferation (pā€Š=ā€Š0.001), and included NOG, KDR, and ANKRD1. The second network (14 genes) included genes important for cellular migration (p<0.001) and angiogenesis (p<0.01). In addition, gene networks associated with cellular migration and adhesion made up a large proportion of the profile which was expected due to the specific aim of the study. These gene networks included MYH6, ICAM5, KDR, CDH4, and AKAP5, which are important for regulating cellular elongation and filopodia extension to enable cellular mobility, as well as NR2E1 whose gene product interacts with the fibronectin matrix during cellular migration, in addition to WISP1 and PAX3 which have been implicated in the epithelial-to-mesenchymal (EMT) transition important for the distant spread of micrometastatic tumor cells. Of the remaining four genes, two genes were outside these networks, and two genes were not annotated.


A prognostic gene expression profile that predicts circulating tumor cell presence in breast cancer patients.

Molloy TJ, Roepman P, Naume B, van't Veer LJ - PLoS ONE (2012)

Network analysis of CTC-profile genes indicted two main functional networks: a cellular survival/proliferation associated network (colored orange) and a cellular migration/angiogenesis related network (colored purple).CTC-profile genes are indicated by grey symbols.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285692&req=5

pone-0032426-g004: Network analysis of CTC-profile genes indicted two main functional networks: a cellular survival/proliferation associated network (colored orange) and a cellular migration/angiogenesis related network (colored purple).CTC-profile genes are indicated by grey symbols.
Mentions: Functional annotation and gene network analysis demonstrated two main networks comprising 29 of the 34 CTC-profile genes (Figure 4). One network (16 genes) was enriched for genes associated with cellular survival and proliferation (pā€Š=ā€Š0.001), and included NOG, KDR, and ANKRD1. The second network (14 genes) included genes important for cellular migration (p<0.001) and angiogenesis (p<0.01). In addition, gene networks associated with cellular migration and adhesion made up a large proportion of the profile which was expected due to the specific aim of the study. These gene networks included MYH6, ICAM5, KDR, CDH4, and AKAP5, which are important for regulating cellular elongation and filopodia extension to enable cellular mobility, as well as NR2E1 whose gene product interacts with the fibronectin matrix during cellular migration, in addition to WISP1 and PAX3 which have been implicated in the epithelial-to-mesenchymal (EMT) transition important for the distant spread of micrometastatic tumor cells. Of the remaining four genes, two genes were outside these networks, and two genes were not annotated.

Bottom Line: The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer.In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome.This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

ABSTRACT
The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into "good prognosis" or "poor prognosis" are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the "CTC profile" also provided prognostic information independent of the well-established and powerful '70-gene' prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays.

Show MeSH
Related in: MedlinePlus