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

ABSTRACT: Development of a primary tumor gene expression profile that can predict the presence of circulating tumor cells in the blood of breast cancer patients. 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31364 | GEO | 2012/04/12

SECONDARY ACCESSION(S): PRJNA145883

REPOSITORIES: GEO

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

Project description:Development of a primary tumor gene expression profile that can predict the presence of circulating tumor cells in the blood of breast cancer patients. 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. Seventy-two primary breast cancer tumor have been analyzed against a breast cancer reference pool.

2012-04-11 | E-GEOD-31364 | biostudies-arrayexpress

Single-nucleotide polymorphism array analysis reveals distinct chromosomal aberrations in breast cancer tumors according to the circulating tumor cells status

Project description:Recent technological advances have made it possible to detect circulating breast cancer cells as precursors of distant metastasis and as prognosis marker in nonmetastatic breast cancer patients. Association of circulating tumor cells (CTCs) with molecular alteration in the primary tumor is not widely explored. We reported differential profile of altered genome, copy number alteration and copy-neutral loss of heterogeneity in 14 primary tumors when comparing patients with CTCs+ versus CTCs- using single-nucleotide polymorphism array. The most prevalent copy number alteration in CTCs+ patients was at 8q and particularly at the cytoband 8q24 (MYC loci). As the role of MYC in the process of tumor cell invasion and migration is controversial, we further validated in a larger series of patients whether altered MYC (amplification or gained) in primary tumors was correlated with the presence of CTCs in peripheral blood (as a surrogate of micrometastais).Â No correlation between MYC alteration and presence of CTCs was observed, providing clinical support to the recent data that MYC suppresses cancer metastasis or at least suggesting that MYC alteration could be contributory but insufficient for the generation of CTCs. This molecular association needs to be further characterized in preclinical model and especially clinically. We analyzed CN and LOH of CTC+ and CTC-

2014-11-19 | E-GEOD-43149 | biostudies-arrayexpress

Isolation and expression profiling of circulating tumor cells in breast cancer patients part 1

Project description:We developed a method to isolate pure circulating tumor cells (CTC). RNA from such CTCs isolated from the peripheral blood of metastatic breast cancer patients and gene expression was performed using cDNAmicroarray. we used cDNA array to compare gene expression of CTCs with normal epithelial and breast tumor samples normal blood vs. breast tumor

2014-12-18 | E-GEOD-45962 | biostudies-arrayexpress

Isolation and expression profiling of circulating tumor cells in breast cancer patients part 3

Project description:We developed a method to isolate pure circulating tumor cells (CTC). RNA from such CTCs isolated from the peripheral blood of metastatic breats cnacer patients and gene expression was performed using cDNAmicroarray. we used cDNA array to compare gene expression of CTCs with normal epithelial and breast tumor samples CTCs vs. breast tumors

2014-12-18 | E-GEOD-45964 | biostudies-arrayexpress

Transcription profiling of circulating tumor cells (CTC) from peripheral blood from patients with breast and prostate cancer

Project description:In many patients with solid tumors circulating tumor cells (CTCs), that form metastases, can be identified in peripheral blood. Detection and characterization of CTCs in cancer patients provide a unique opportunity to predict patient survival, select and monitor the efficacy of treatment as well as to gain insights into the cascade of metastatic events. Here, we describe a novel approach to identify CTC-specific molecular markers. Using an integrated platform for immunomagnetic enrichment and immunofluorescent identification of CTCs, blood samples with large numbers of CTCs were identified from patients with colorectal, prostate and breast cancers. Despite enrichment, CTCs are still outnumbered by "nonspecifically" captured leukocytes. In order to determine gene expression profile for CTCs, "background" gene expression signature of white blood cells must be taken into account. To this end, following enrichment for CTCs, RNA was also extracted from the remaining CTC-depleted blood samples. The following samples were used to generate the global expression profiles for CTCs: 1a) SAMPLE170711SUB735: CTC-enriched blood sample from a patient with breast cancer). 3700 CTCs were identified per 7.5 ml of peripheral blood in this patient. 1b) SAMPLE170712SUB735: Corresponding CTC-depleted blood sample for the above patient with breast cancer. 2a) SAMPLE170829SUB750: CTC-enriched blood sample from a patient with prostate cancer. 647 CTCs were identified per 7.5 ml of peripheral blood in this patient. 2b) SAMPLE170830SUB750: Corresponding CTC-depleted blood sample for the above patient with prostate cancer. 3a) SAMPLE170831SUB751: CTC-enriched sample from a patient with colorectal cancer. 180 CTCs were identified per 7.5 ml of peripheral blood in this patient. 3b) SAMPLE170832SUB751: Corresponding CTC-depleted blood sample for the above patient with colorectal cancer.

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Circulating Tumor Cell Clusters are Oligoclonal Precursors of Breast Cancer Metastasis

Project description:Clusters of circulating tumor cells (CTC-clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Here, we first use mouse models to demonstrate that breast cancer cells injected intravascularly as clusters are more prone to survive and colonize the lungs than single cells. Primary mammary tumors comprised of tagged cells give rise to oligoclonal CTC-clusters, with 50-fold increased metastatic potential, compared with single CTCs. Using intravital imaging and in vivo flow cytometry, CTC-clusters are visualized in the tumor circulation, and they demonstrate rapid clearance in peripheral vessels. In patients with breast cancer, presence of CTC-clusters is correlated with decreased progression-free survival. RNA sequencing identifies the cell junction protein plakoglobin as most differentially expressed between clusters and single human breast CTCs. Expression of plakoglobin is required for efficient CTC-cluster formation and breast cancer metastasis in mice, while its expression is associated with diminished metastasis-free survival in breast cancer patients. Together, these observations suggest that plakoglobin-enriched primary tumor cells break off into the vasculature as CTC-clusters, with greatly enhanced metastasis propensity. RNA-seq from 29 samples (15 pools of single CTCs and 14 CTC-clusters) isolated from 10 breast cancer patients

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Isolation and expression profiling of circulating tumor cells in breast cancer patients part 2

2014-12-18 | E-GEOD-45963 | biostudies-arrayexpress

Molecular profiling of peripheral blood is associated with circulating tumor cells content and poor survival in metastatic castration-resistant prostate cancer

Project description:The enumeration of circulating tumor cells (CTCs) in peripheral blood correlates with clinical outcome in castration-resistant prostate cancer (CRPC). We analyzed the molecular profiling of peripheral blood from 43 metastatic CRPC patients with known CTC content in order to identify genes that may be related to prostate cancer progression. Global gene expression analysis identified the differential expression of 282 genes between samples with ?5 CTCs vs <5 CTCs, 58.6% of which were previously described as over-expressed in prostate cancer (18.9% in primary tumors and 56.1% in metastasis). Those genes were involved in survival functions such as metabolism, signal transduction, gene expression, and cell growth, death, and movement. The expression of selected genes was evaluated by quantitative RT-PCR. This analysis revealed a two-gene model (SELENBP1 and MMP9) with a high significant prognostic ability (HR 6; 95% CI 2.61 - 13.79; P<0.0001). The combination of the two-gene signature plus the CTCs count showed a higher prognostic ability than neither CTCs enumeration nor gene expression alone (P<0.05). This study shows a gene expression profile in PBMNC is associated with CTCs count and clinical outcome in metastatic CRPC, describing genes and pathways potentially associated with CRPC progression. The complete database comprised the expression measurements of 43 metastatic castration-resistant prostate cancer (CRPC) samples and their asociation with the number of circulating tumor cells (CTCs). Twenty of them have a number circulating tumor cells (CTCs) greater than 5.

2015-04-30 | E-GEOD-66532 | biostudies-arrayexpress

Isolation and expression profiling of circulating tumor cells in breast cancer patients part 1

2014-12-18 | GSE45962 | GEO

Reanalysis of transcriptomic profiling of isolated CTC from 31 patients

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