Genomic alterations and transcriptional phenotypes in circulating tumor DNA and matched metastatic tumor
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1125930 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We profiled the tumor heterogeneity of individual primary tumor and matched metastatic cells of breast cancer using a set of patient derived xenograft models with different metastatic potentials. This data set gives insights into the transcriptional tumor heterogeneity, the transcriptional differences between primary tumor and matched metastatic cells and how these are changing in regard to varying metastatic phenotypes.
2022-08-15 | GSE211146 | GEO
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. We profiled RNA from 75 single cells circulating in mouse blood enriched for circulating tumor cells from 5 mice, 12 single cells from a mouse embryonic fibroblast cell line, 16 single cells from the nb508 mouse pancreatic cancer cell line, 12 single mouse white blood cells, 18 single GFP lineage-traced circulating tumor cells from two mice, 20 single GFP lineage-traced cancer cells from the primary pancreatic tumor of a mouse, and 34 dilutions to 10 or 100 picograms of total RNA from mouse primary pancreatic tumors from 4 mice.
2014-09-22 | E-GEOD-51372 | biostudies-arrayexpress
Project description:Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for multi-omic profiling remains widely unexplored. Here, we pursued next-generation sequencing of circulating EV-DNA and EV-RNA in metastatic prostate cancer (mPC), using a range of in-vitro and in-vivo models, validating our findings in 35 mPC patients with longitudinal samples collected during androgen receptor signaling inhibitor (ARSI) therapy. EV-DNA copy-number (CN) profiles matched same-patient biopsies and ctDNA (p<0.001) and EV-DNA tumor fraction (TF) associated with shorter time to progression. We developed a novel approach for studying mRNA in circulating EVs (RExCuE), showing high correlation between EV-RNA and tumor biopsies (r>0.7, p<0.001). EV-RNAseq signatures at 4 weeks of therapy associated with clinical responses. Last, we derived a specific signature of ARSI response in EV-RNA in vivo that predicted response to therapy. In conclusion, EV profiling enables the study of mPC evolution at transcriptomics level in liquid biopsies.
2024-06-30 | GSE221709 | GEO
Project description:Self-sufficiency (autonomy) in growth signaling, the earliest recognized hallmark of cancer, is fuelled by the tumor cell’s ability to ‘secrete-and-sense’ growth factors; this translates into cell survival and proliferation that is self-sustained by auto-/paracrine secretion. Using breast cancer cells that are either endowed or inept in growth signaling autonomy, here we reveal how tumor cell autonomy impacts cancer progression. Autonomy is associated with enhanced molecular programs for stemness, immune evasiveness, and epithelial-mesenchymal plasticity (EMP) across the entire mesenchymal spectrum. Autonomy is both necessary and sufficient for anchorage-independent growth factor-restricted growth, resistance to anti-cancer drugs and metastatic progression. Transcriptomic and proteomic studies show that autonomy is associated with self-sustained EGFR/ERBB signaling, a required signal for re-epithelialization. A gene expression signature was derived (a.k.a., autonomy signature) which revealed that autonomy is induced in circulating tumor cells (CTCs), the precursor tumor cells that re-epithelialize to initiate metastases. Autonomy in CTCs tracks therapeutic response and prognosticates outcome. Autonomy is present during reversible (but not stable) EMT and requires EGFR/ERBB signaling. These data support a role for growth signaling autonomy in the blood-borne dissemination of human breast cancer.
2023-02-06 | PXD037253 | Pride
Project description:Metastasis accounts for the majority of all cancer deaths, yet the process remains poorly understood. A pivotal step in the metastasis process is the exiting of tumor cells from the circulation, a process known as extravasation. However, it is unclear how tumor cells extravasate, and if multicellular clusters of tumor cells posses the ability to exit as a whole or must first disassociate. In this study, we use in vivo zebrafish and mouse models to elucidate the mechanism tumor cells use to extravasate. We found that circulating tumor cells exit the circulation using the recently identified extravasation mechanism, angiopellosis, and do as both clusters and individual cells. We further show that when melanoma and cervical cancer cells utilize this extravasation method to exit as clusters, they exhibit an increased ability to form tumor at distant sites through the expression of unique genetic profiles. Collectively, we present a new model for tumor cell extravasation of both individual and multicellular circulating tumor cells.
2019-08-26 | GSE132583 | GEO
Project description:Growth Signaling Autonomy in Circulating Tumor Cells Aids Metastatic Seeding
| PRJNA890663 | ENA
Project description:<p>Circulating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the 'best' indicator of metastatic risk because their heterogeneity is generally neglected. In this study, we develop a molecular typing system to predict colorectal cancer metastasis potential based on the metabolic fingerprints of single CTCs. After identification of the metabolites potentially related to metastasis using mass spectrometry-based untargeted metabolomics, setup of a home-built single-cell quantitative mass spectrometric platform for target metabolite analysis in individual CTCs and use of a machine learning method composed of non-negative matrix factorization and logistic regression, CTCs are divided into two subgroups, C1 and C2, based on a 4-metabolite fingerprint. Both <em>in vitro</em> and <em>in vivo</em> experiments demonstrate that CTC count in C2 subgroup is closely associated with metastasis incidence. This is an interesting report on the presence of a specific population of CTCs with distinct metastatic potential at the single-cell metabolite level. </p>
2023-08-21 | MTBLS5028 | MetaboLights
Project description:Metastatic colorectal cancer (mCRC) relies on the detachment of aggressive malignant cells from the primary tumor into the bloodstream, these Circulating Tumor Cells (CTC) being the principal source of the further metastasis. Here, we approached the massive molecular profiling of the CTC population isolated from mCRC patients. Clinically, the presence of CTC is associated with poor prognosis and there exists a clear necessity for more specific and efficient chemotherapies in the treatment of mCRC. Immunoisolation of CTC from these patients combined with a whole transcriptome amplification and hybridization onto gene expression arrays, lead us to specifically describe for the first time a CTC population with adhesive and migratory characteristics, in addition to a modulated expression of genes related to cell death and survival. Furthermore, bioinformatic analysis provided with an armamentarium of highly specific and sensitive valuable markers that should impact on the management and follow-up of mCRC patients. Finally, molecular profiling of CTC resulted in the identification of new therapeutic targets, like TGF-β1 impairing, specifically targeting the CTC population which should improve the efficacy in the eradication and prevention of CRC metastasis. In conclusion, molecular profiling of CTC represents an innovative and promising approach in the clinical management of mCRC patients. Circulating Tumor Cells (CTC) were immunoisolated from six metastatic colorectal patients (mCRC). Moreover, blood from three healthy donors were obtained, immunoisolating non-specific cellularity background. RNA was extracted and globally amplified with a Whole Transcriptome Amplification system. Samples were hybridized onto agilent arrays and CTC specific genes were obtained. Gene networks were built with IPA software and a gene ontology analysis was performed. Eleven candidate genes were validated by real time PCR. Finally, TGFB1 was evaluated as a potential drugable target against CTC population.
2012-06-29 | E-GEOD-31023 | biostudies-arrayexpress
Project description:Comparison of gene expression profiles between a primary melanoma and an early metastatic specimen from the same patient will provide essential biological insight into early metastatic processes. The DASL (cDNA mediated annealing, selection, extension and ligation) assay has been used to generate gene expression data for 502 cancer-related genes from very small formalin-fixed sentinel node biopsy (SNB) melanoma samples, this data has been further compared with gene expression of the matched formalin-fixed primary melanoma. Tissue was sampled from twenty-five SNB deposits using laser capture microdissection. The mean number of genes detected using DASL with SNB samples was lower than when using a core of primary melanoma tumor (242 versus 434 genes). A large proportion of SNB samples failed (<240 genes detected) the assay (57.7%). Area of tissue microdissected, RNA concentration and qRT-PCR quality control did not predict performance of samples on the array but age of sampled tissue negatively correlated with number of genes detected (p=0.01). For samples that performed successfully, matched primary samples were available for 10 samples. Gene expression profiles correlated between all matched tumor pairs (Spearman’s rho 0.15-0.80, p<0.01), although a number of genes were differentially expressed between nodal and primary tumors in all tumor pairs. This study demonstrates that the DASL assay can be used to generate gene expression data from small formalin-fixed samples, but not consistently. Differentially expressed genes were identified across 10 matched primary and nodal tumor pairs suggesting that the DASL assay could be used to derive essential biological information about early metastasis.
2011-08-02 | GSE31139 | GEO
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