Ontology highlight
ABSTRACT:
PROVIDER: PRJNA764061 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15928564_1.fastq.gz | Fastqsanger.gz | |||
| SRR15928564_2.fastq.gz | Fastqsanger.gz | |||
| SRR15928565_1.fastq.gz | Fastqsanger.gz | |||
| SRR15928565_2.fastq.gz | Fastqsanger.gz | |||
| SRR15928566_1.fastq.gz | Fastqsanger.gz |
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Project description:Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC-clusters). Existing technologies for CTC enrichment are designed primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here, we developed a microchip technology (Cluster-Chip) specifically designed to capture CTC-clusters independent of tumor-specific markers from unprocessed blood. CTC-clusters are isolated through specialized bifurcating traps under low shear-stress conditions that preserve their integrity and even two-cell clusters are captured efficiently. Highly parallel architecture of the chip allows deterministic screening of clinically relevant volumes of blood samples at slow, and hence, non-damaging flow rates. Using the Cluster-Chip, we identify CTC-clusters in 30-40% of patients with metastatic cancers of the breast, prostate and melanoma. RNA sequencing of CTC-clusters confirms their tumor origin and identifies leukocytes within the clusters as being tissue-derived macrophages. Together, the development of a device for efficient capture of CTC-clusters will enable detailed characterization of their biological properties and role in cancer metastasis. We used the Cluster-Chip to capture CTC-clusters from the blood of a breast cancer patient with high CTC counts, released CTC-clusters in solution, stained them with TexasRed-conjugated antibodies against the leukocyte cell surface markers CD45, CD14 and CD16, and then isolated intact CTC-clusters individually using a micromanipulator. From a single time point, we retrieved 15 CTC-clusters, and each of those clusters was individually subjected to RNA-sequencing analysis using a next generation platform (SOLiD 5500). In addition, two leukocytes were isolated from the blood of a healthy donor were individually subjected to RNA-sequencing analysis using the same platform.
2015-05-17 | E-GEOD-67939 | biostudies-arrayexpress
Project description:Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC-clusters). Existing technologies for CTC enrichment are designed primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here, we developed a microchip technology (Cluster-Chip) specifically designed to capture CTC-clusters independent of tumor-specific markers from unprocessed blood. CTC-clusters are isolated through specialized bifurcating traps under low shear-stress conditions that preserve their integrity and even two-cell clusters are captured efficiently. Highly parallel architecture of the chip allows deterministic screening of clinically relevant volumes of blood samples at slow, and hence, non-damaging flow rates. Using the Cluster-Chip, we identify CTC-clusters in 30-40% of patients with metastatic cancers of the breast, prostate and melanoma. RNA sequencing of CTC-clusters confirms their tumor origin and identifies leukocytes within the clusters as being tissue-derived macrophages. Together, the development of a device for efficient capture of CTC-clusters will enable detailed characterization of their biological properties and role in cancer metastasis.
2015-05-17 | GSE67939 | 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: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:Background and aims: Immune checkpoint inhibitors have promising outcomes in patients with hepatocellular carcinoma (HCC); however, there is no reliable biomarker for predicting disease progression. Circulating tumor cells (CTCs) derived from peripheral blood have attracted attention in monitoring therapeutic efficacy. In this study, CTCs were serially collected from patients with HCC undergoing atezolizumab plus bevacizumab (Atezo+Bev) treatment, and changes in molecular expression and CTC numbers were analyzed to identify effective biomarkers. Approach and results: The peripheral blood samples were collected serially from 22 patients with HCC treated with Atezo+Bev, and CTCs were enriched using RosetteSep. The CD45(-)PanCK(+) cell counts were measured using flow cytometry. RNA extracted from enriched CTCs underwent targeted RNA sequencing with next-generation sequencing (NGS) and performed unsupervised hierarchical clustering analysis. Changes in CTC numbers during Atezo+Bev treatment reflected the tumor volume. NGS analysis revealed that patients with elevated transforming growth factor (TGF)-β signaling molecules had a poorer response, whereas those with elevated apoptosis signaling molecules had a favorable response (p < 0.05). In addition, compared with changes in CTC counts, changes in TGF-β signaling molecule expression in CTCs accurately and promptly predicted treatment response. Conclusions: NGS analysis of CTC-derived RNA showed that changes in TGF-β signaling molecules predict treatment response earlier than changes in CTC counts. These findings suggest that changes in the expression of TGF-β molecules in CTCs could serve as novel biomarkers for the early prediction of therapeutic response in patients with unresectable HCC undergoing Atezo+Bev therapy.
2024-07-17 | GSE261186 | GEO
Project description:The miR-23a-27a-24-2 cluster is overexpressed in human cancers, including hepatocellular carcinoma (HCC). However, the role of three mature miRNAs of the miR-23a-27a-24-2 cluster in HCC is still controversial. Also, the integrative role of the miR-23a-27a-24-2 cluster in HCC remains elusive. In the present study, using CRISPR knockout (KO), CRISPR interference (CRISPRi), and CRISPR activation (CRISPRa) technologies, we established an endogenous miR-23a-27a-24-2 controllable and various knockout (KO) cell models, which were used to dissect the functional role and underlying signaling of the miR-23a-27a-24-2 cluster. Either miR-23a KO or miR-27a KO reduced cell growth in vitro and in vivo. Of particular note, endogenous miRNAs in the miR-23a-27a-24-2 cluster were effectively regulated by CRISPRi/a, identifying an integrated oncogenic role of the miR-23a-27a-24-2 cluster in HCC cells. Functional analysis showed that miR-23a KO and miR-27a KO led the cell cycle arrest, especially at the G2/M phase, by reducing CDK1/cyclin B activation in HCC cells. Furthermore, a high-throughput RNA-seq approach with miRNA target prediction identified the miR-23a/miR-27a-regulated gene network, further validated by various technologies. In addition, miR-23a and miR-27a have opposite roles in cell migration and mesenchymal-epithelial transition. However, an integrated analysis by CRISPRi/a suggested an oncogenic role of the miR-23a-27a-24-2 cluster in cell migration, which may require a miR-23a-BMPR2-Smad-Snail axis in HCC cells. Thus, our CRISPRi/a study offers a valuable research tool for dissecting the integrated role and underlying mechanism of an endogenous miRNA cluster. Also, this CRISPR approach may provide new routes of miRNA intervention for miRNA targeted therapy.
2024-09-30 | GSE199332 | GEO
Project description:The presence of circulating tumor cell (CTC) clusters is associated with disease progression, new metastasis formation and reduced survival in a variety of cancer types. In breast cancer, pre-clinical studies showed that inhibitors of the Na+/K+-ATPase can suppress CTC clusters shedding and block metastasis. Here, we conducted a prospective, open-label, phase I study in patients with metastatic breast cancer, where the primary endpoint was to determine whether a short (one week) treatment with the Na+/K+-ATPase inhibitor digoxin could reduce mean CTC cluster size. Mechanistically, transcriptome profiling of CTCs highlighted downregulation of cell-cell adhesion and cell cycle-related genes upon treatment with digoxin, in line with its cluster-dissolution activity. ClinicalTrials.gov identifier: NCT03928210.
2024-12-06 | GSE249233 | GEO
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
2014-07-11 | E-GEOD-51827 | biostudies-arrayexpress
Project description:Circulating tumor cells (CTCs) are precursors of metastasis in several cancer types, and are occasionally found within the bloodstream in association with non-malignant cells such as white blood cells (WBCs). The identity and function of these CTC-associated WBCs, as well as the molecular features that define the interaction between WBCs and CTCs are unknown. Here, we achieve the isolation and interrogation of individual CTC-associated WBCs, alongside with corresponding cancer cells within each CTC-WBC-cluster, from multiple breast cancer patients and mouse models.
2019-02-06 | GSE109761 | GEO