Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA255097 | ENA |
REPOSITORIES: ENA
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Project description:Liquid biopsies are becoming imperative on early patient diagnosis, prognosis and evaluation of residual disease. The use of circulating extracellular vesicles (EVs) as surrogate markers of tumor progression could be a powerful tool in the clinical setting. EVs in plasma have emerged as a non-invasive option to detect metastatic outcome, however sensitivity is low. Here we have characterized the lymph obtained after postoperative lymphadenectomy as a novel biological fluid enriched in EVs. Our proteomic profiling and BRAFV600E/K status determination demonstrate for the first time that EVs from the lymph of melanoma patients are enriched in melanoma-associated proteins and are useful for BRAF mutations detection. Melanoma oncogenic pathways, immunomodulation and platelet activating proteins are enriched in lymph-derived exosomes from patients with distal lymph node spread compared to local/early spreading. Furthermore, patients positive for BRAFV600E mutation on lymph-circulating vesicles had a shorter time of relapse. These data encourage the analysis of lymph-circulating EVs for detection of residual disease and recurrence.
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Project description:In order to improve our understanding of microRNA (miRNA) deregulation in melanoma development and possible consequences for patient survival, miRNA expression profiles were determined, using an array based approach, in melanoma tumors, melanoma cell lines and normal melanocytes. Differentially expressed miRNAs were evaluated in relation to clinical characteristics, patient prognosis in terms of melanoma-specific survival, and mutational status for BRAF and NRAS.
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Project description:Inhibition of immune-checkpoint targets including PD1 is clinically effective in a variety of cancers. However, only a subset of patients respond and complete response remains uncommon. Given the known role of metabolites in modulating immunity, we sought to understand how individual patients’ metabolic activities adapt to PD1 immune checkpoint blockade and how they associate with therapeutic benefits. To this end, we profiled metabolites in pre- and multiple on-treatment patient serum samples from three independent immunotherapy trials using hydrophilic interaction liquid chromatography coupled with either triple quadrupole MS multiple reaction monitoring or high resolution full scan MS detection. The study consisted of two Phase I trials (CA209-038, NCT01621490; CA209-009, NCT01358721) which included 78 patients with advanced melanoma and 91 patients with metastatic renal cell carcinoma (RCC) treated with nivolumab. To investigate the generalizability of our results, we also analyzed a large randomized Phase III trial (CheckMate 025, NCT01668784) with 743 RCC patients, among which 394 received nivolumab and 349 received everolimus. V600E is the most common BRAF mutation in melanoma and BRAF_V600E indicates the mutation status.
2019-08-12 | ST001236 | MetabolomicsWorkbench
Project description:Liquid biopsies are becoming imperative on early patient diagnosis, prognosis and evaluation of residual disease. The use of circulating extracellular vesicles (EVs) as surrogate markers of tumor progression could be a powerful tool in the clinical setting. EVs in plasma have emerged as a non-invasive option to detect metastatic outcome, however sensitivity is low. Here we have characterized the lymph obtained after postoperative lymphadenectomy as a novel biological fluid enriched in EVs. Our proteomic profiling and BRAFV600E/K status determination demonstrate for the first time that EVs from the lymph of melanoma patients are enriched in melanoma-associated proteins and are useful for BRAF mutations detection. Melanoma oncogenic pathways, immunomodulation and platelet activating proteins are enriched in lymph-derived exosomes from patients with distal lymph node spread compared to local/early spreading. Furthermore, patients positive for BRAFV600E mutation on lymph-circulating vesicles had a shorter time of relapse. These data encourage the analysis of lymph-circulating EVs for detection of residual disease and recurrence.ADDENDUM: After the proper verification of the cell lines analysed in this dataset where it is written "SKMel103" or "SK103", it should be read as "SKMel147". This affects not only the raw files but also all the search results files. Sorry for the inconveniences.
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Project description:A panel of 17 human melanoma cell lines with known BRAF and NRAS mutation status was stimulated with TNF-alpha for 72 hours. The goal of the study was to correlate the transcriptional response in BRAF versus NRAS mutated melanoma cell lines.
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Project description:To determine how mutation of BRAF affected the response to RAF265, we utilized a tumor orthotopic implant model of early passage melanoma tumors in nude mice from a series of 17 patients with advanced metastatic Tumor growth was compared between RAF265 treatment (40 mg/kg, QD) and diluent control groups. The melanoma associated gene mutation profile and global gene expression profile were determined on these human melanoma samples by SNaPshot and Affymetrix Human Gene ST 1.0 Array, respectively. Tumors were evaluated for growth response to RAF265 in an orthotopic implant model using nude mice. Comparisons were made between gene expression profiles of responders and non-responders, BRAF mutant and BRAF wild type tumors. Analysis of the microarray data revealed responders exhibited enriched expression of genes involved in cell cycle, apoptosis, cell-cell adhesion and initiation of epithelial/mesenchymal transition. It is concluded that RAF265 significantly inhibits the growth of a sub-population of V600E mutant and wild type BRAF human melanoma tumors in vivo and the gene expression profile of this subset of tumors that may predict response to RAF265. RNA from 17 human metastatic melanoma tumors was extracted and hybridized on Affymetrix microarrays.
2012-05-01 | E-GEOD-30812 | biostudies-arrayexpress
Project description:In order to improve our understanding of microRNA (miRNA) deregulation in melanoma development and possible consequences for patient survival, miRNA expression profiles were determined, using an array based approach, in melanoma tumors, melanoma cell lines and normal melanocytes. Differentially expressed miRNAs were evaluated in relation to clinical characteristics, patient prognosis in terms of melanoma-specific survival, and mutational status for BRAF and NRAS. Agilent microarray platform containing 470 miRNAs was used to determine miRNA expression profiles in 3 normal melanocytes (as non-neoplastic control), 21 melanoma cell lines and 16 clinical samples from fresh frozen regional lymph node metastases. To validate the microarray platform, the expression levels of some miRNAs were evaluated using RT-PCR and the correlation between the two platforms was assessed using Pearson Correlation analysis. The results obtained were further verified and confirmed by RT-PCR in an independent set of melanoma samples. Association between deregulated miRNAs and survival was determined by Univariate Cox proportional hazards model and log rank test.
2010-04-21 | E-GEOD-19387 | biostudies-arrayexpress
Project description:A panel of 17 human melanoma cell lines with known BRAF and NRAS mutation status was stimulated with TNF-alpha for 72 hours. The goal of the study was to correlate the transcriptional response in BRAF versus NRAS mutated melanoma cell lines. Total RNA was obtained from a panel of 17 human melanoma cell lines treated for 72 hours with TNF-alpha or left untreated. Gene expression profiling was done using the Illumina Human HT12 v4 platform.
2014-02-10 | E-GEOD-51221 | biostudies-arrayexpress