Reanalysis of transcriptomic profiling of isolated CTC from 31 patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE215886 | GEO | 2023/06/20
REPOSITORIES: GEO
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Project description:Circulating tumor cells (CTCs) play a fundamental role in cancer progression. However, in mice, limited blood volume and the rarity of CTCs in the bloodstream preclude longitudinal, in-depth studies of these cells using existing liquid biopsy techniques. Here, we present an optofluidic system that continuously collects fluorescently-labeled CTCs from a genetically-engineered mouse model for several hours per day over multiple days or weeks. The system is based on a microfluidic cell-sorting chip connected serially to an un-anesthetized mouse via an implanted arteriovenous shunt. Pneumatically-controlled microfluidic valves capture CTCs as they flow through the device and CTC-depleted blood is returned back to the mouse via the shunt. To demonstrate the utility of our system, we profile CTCs isolated longitudinally from animals over a four-day treatment with the BET inhibitor JQ1 using single-cell RNA-Seq (scRNA-Seq) and show that our approach eliminates potential biases driven by inter-mouse heterogeneity that can occur when CTCs are collected across different mice. The CTC isolation and sorting technology presented here provides a research tool to help reveal details of how CTCs change over time, allowing studies to credential changes in CTCs as biomarkers of drug response and facilitating future studies to understand the role of CTCs in metastasis.
2018-12-31 | GSE122233 | GEO
Project description:Circulating Tumor Cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. To determine the relevance of ECM protein expression to human disease, CTCs were isolated from the blood of metastatic PDAC patients and subjected to single cell RNA-sequencing. Analysis of 7 pancreatic CTCs from 3 patients revealed that the majority expressed keratins defining their epithelial origin. A total of 13 of 60 extracellular protein genes enriched in mouse CTCs (see GEO GSE51372) were expressed at high levels (>100 rpm) in at least one human pancreatic CTC. Human SPARC was the only gene found at high levels in all human pancreatic CTCs. To achieve a deep RNA sequencing profile of CTCs at the single cell level, we applied a novel inertial focusing-enhanced device, the CTC-iChip, which allows high efficiency negative depletion of normal blood cells, leaving unattached CTCs in solution where they can be selected and analyzed as single cells (Pubmed ID 23552373). CTCs were then subjected to single cell RNA-sequencing (Pubmed ID 20203668).
2014-09-22 | E-GEOD-60407 | biostudies-arrayexpress
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:<br><br> 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.<br> 1b) SAMPLE170712SUB735: Corresponding CTC-depleted blood sample for the above patient with breast cancer.<br> 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.<br> 2b) SAMPLE170830SUB750: Corresponding CTC-depleted blood sample for the above patient with prostate cancer.<br> 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.<br> 3b) SAMPLE170832SUB751: Corresponding CTC-depleted blood sample for the above patient with colorectal cancer.
2005-06-30 | E-MEXP-136 | biostudies-arrayexpress
Project description:We report RNA sequencing data from enriched prostate circulating tumor cells (CTCs) from clinical blood specimens. The goal is to examine the stability of RNA signatures as a function of whole blood preservation. Each blood sample was split into two equal portions; one portion was processed immediately (i.e., 0 hour) for CTC isolation; the other was preserved in 4 deg C, using methods described in this publication, for 24, 48, or 72 hours prior to CTC isolation. CTCs were isolated using the CTC-iChip and processed for RNA sequencing.
2017-10-08 | GSE104209 | GEO
Project description:Circulating tumor cell clusters/micro-emboli (CTM) possess greater metastatic capacity and survival advantage compared to individual circulating tumor cell (CTCs). However, the formation of CTM subtypes and their role in tumor metastasis remain unclear. In this study, we used a microfluidic Cluster-chip with easy operation and high efficiency to isolate CTM from peripheral blood, which confirmed their correlation with clinicopathological features and identified the critical role of CTC-platelet clusters in BC metastasis. The correlation between platelets and CTM function was further confirmed in a mouse model and RNA-seq of CTM identified high-expressed genes related to hypoxia stimulation and platelet activation which possibly suggested the correlation of hypoxia and CTC-platelet cluster formation. In conclusion, we successfully developed the Cluster-chip platform to realize the clinical capture of CTMs and analyze the biological properties of CTC-platelet clusters, which could benefit the design of potential treatment regimens to prevent CTM-mediated metastasis and tumor malignant progression.
2024-02-28 | GSE256445 | GEO
Project description:Unraveling the yet unknown molecular mechanisms regulating the biology of metastasis-competent Circulating Tumor Cells (CTCs) is important for better understanding metastatic growth and disease relapses in patients with colon cancer. We investigated and compared the transcriptome profiles of the CTC line and of a cell line derived from a primary colon cancer to get some insight into the specific molecular mechanism of metastasis-competent CTCs. We used microarrays to establish the molecular portrait of the metastasis-competent CTC and of HT-29 cells
2019-06-02 | GSE82198 | GEO
Project description:Extremely rare circulating tumor cell (CTC) clusters are both increasingly appreciated as highly metastatic precursors and virtually unexplored. Technologies are primarily designed to detect single CTCs and often fail to account for the fragility of clusters or to leverage cluster-specific markers for higher sensitivity. Meanwhile, the few technologies targeting CTC clusters lack scalability. Here, we introduce the Cluster-Wells, which combines the speed and practicality of membrane filtration with the sensitive and deterministic screening afforded by microfluidic chips. The >100,000 microwells in the Cluster-Wells physically arrest CTC clusters in unprocessed whole blood, gently isolating virtually all clusters at a throughput of >25 mL/h, and allow viable clusters to be retrieved from the device. Using the Cluster-Wells, we isolated CTC clusters ranging from 2–100+ cells from prostate and ovarian cancer patients and analyzed a subset using RNA sequencing. Routine isolation of CTC clusters will democratize research on their utility in managing cancer.
2022-05-24 | GSE202650 | GEO
Project description:By applying RNA-ISH and RNAseq to circulating tumor cells (CTCs), the study provides definitive evidence of epithelial to mesenchymal transition (EMT) across all histological types of breast cancer, identifying mediators such as FOXC1 and TGF-β signaling, and demonstrating dynamic treatment-associated changes in EMT within clusters of CTCs. Epithelial to mesenchymal transition (EMT) has been postulated to contribute to the migration and dissemination of cancer cells, but supporting histopathological evidence is limited. We used a microfluidic device to isolate circulating tumor cells (CTCs), combined with multiplex fluorescent RNA-in-situ hybridization (ISH) and RNA sequencing, to quantify and characterize EMT in breast cancer cells within the bloodstream. Whereas only rare (0.1-10%) cells in the primary tumor expressed both mesenchymal and epithelial markers, such biphenotypic as well as purely mesenchymal cells were enriched among CTCs, across all histological subtypes of breast cancer. In an index patient followed longitudinally, fluctuation in epithelial and mesenchymal states was observed as a function of initial response and subsequent resistance to therapy. Mesenchymal markers were predominant in clusters of tumor cells, many of which had adherent platelets. Finally, RNA sequencing of CTC clusters identified TGF-β and other EMT-related signatures, which were absent from more epithelial CTCs. FOXC1, a known regulator of EMT, was abundantly expressed in mesenchymal CTCs and was detectable within localized regions of the primary breast tumor. Together, these data support a role for EMT in the blood-borne dissemination of breast cancer and point to the dynamic nature of this cell fate change.
2013-02-01 | E-GEOD-41245 | biostudies-arrayexpress
Project description:Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice, rapidly declining after B-RAF inhibitor treatment. CTCs were shed early from localized tumors and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled comparison of RNA sequencing profiles with the matched primary tumor. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. In patients with metastatic melanoma, CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF targeted therapy. Together, the capture of CTCs and their molecular characterization provide insight into the hematogenous spread of melanoma. We adapted a microfluidic platform, the HbCTC-Chip (Stott et al., 2010, Pubmed ID: 20930119), to capture melanoma CTCs derived from mouse tumors, using panels of antibodies against melanoma-specific cell surface markers, followed by staining for melanoma antigens and optimized on-chip fluorescent imaging. We used a tamoxifen inducible BRAF(CA/+)/PTEN(flox/flox) melanoma mouse model (Dankort et al., 2009, Pubmed ID: 19282848) derived from a C57BL/6 background. Such mice received focal subcutaneous injection of tamoxifen (Sigma) (50ul at 5mg/ml in 50% EtOH suspension) at the left flank at 6-7 weeks after birth. Blood samples were collected from five mice with high tumor burden following tamoxifen injection. Blood from each mouse was split and processed through the CTC-chips functionalized with anti-CSPG4/MCAM antibody and control IgGs, respectively. Matched primary (from the tamoxifen injection site) and metastatic (from upper or lower back) tumors were harvested from the same mouse and immediately flash-frozen in liquid nitrogen. RNA extraction, single molecular sequencing and determination of Digital Gene Expression was as in Yu et al., 2012 (Pubmed ID: 22763454). One of the five mice yielded no CTC or IgG data. In addition, skin was taken from a sixth mouse, which was a complete wild type C57BL/6 mouse (without the BRAF/PTEN transgenes).The skin was taken after euthanasia of the animal and was processed as the tissue from the matched primary and metastatic tumors.
2014-03-31 | E-GEOD-52031 | biostudies-arrayexpress
Project description:Circulating Tumor Cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. Using a pancreatic cancer mouse model, we applied a microfluidic device to isolate CTCs independently of tumor epitopes, subjecting these to single cell RNA-sequencing. This study was conducted to determine the heterogeneity of pancreatic CTCs and to compare these CTCs to matched primary tumors, cell line controls (NB508 cancer cell line and MEF non-cancer cell line), primary tumor single cells, and normal leukocytes/WBCs.
2014-09-22 | GSE51372 | GEO