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Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

ABSTRACT: Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

PROVIDER: PRJNA732665 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14640600_1.fastq.gz	Fastqsanger.gz
	SRR14640600_2.fastq.gz	Fastqsanger.gz
	SRR14640700_1.fastq.gz	Fastqsanger.gz
	SRR14640700_2.fastq.gz	Fastqsanger.gz
	SRR14640800_1.fastq.gz	Fastqsanger.gz

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Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

Project description:Diffuse large B-cell lymphoma (DLBCL) is the predominant type in central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of CSF-DLBCs from seven CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathway. CSF-DLBCs within individual patient have monoclonality with similar variable region of light chains (VL) expression. It is interesting to find some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within patient. The transcriptional heterogeneity across CSF-DLBCs are manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

2021-08-25 | GSE175510 | GEO

Phosphoproteome Analysis of Cerebrospinal Fluid Extracellular Vesicles in Primary Central Nervous System Lymphoma

Project description:Primary central nervous system lymphoma(PCNSL) is a rare extra-nodal non-Hodgkin’s lymphoma and accounts for 3%-4% of central nervous system tumors. Recent studies have highlighted the importance of cerebrospinal fluid derived extracellular vesicles in PCNSL. Extracellular vesicles(EVs) are nanoscale vesicles with bilayer lipid membrane released by almost all cell types. EVs are present in body fluids, including urine, blood and CSF. Cerebrospinal fluid(CSF) is a colorless fluid that surrounds the brain and spinal cord and acts as lymph in the central nervous system. CSF-derived EVs contain proteins from neurons, oligodendrocytes, astrocytes and microglias. Studies of CSF EVs are mainly limited by the amount of EVs isolated from per milliliter of CSF and the volume of CSF acquired from one patient. Here, we provide a label-free quantitative phospho-proteome profiling of EVs separated from PCNSL and non-PCNSL CSF samples by an earlier introduced functional magnetic beads called EVTRAP together with highly sensitive timsTOF Pro.

2023-07-12 | PXD040744 | JPOST Repository

Single-cell transcriptome analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma.

Project description:Diffuse large B cells in the cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of central nervous system lymphoma (CNSL) leptomeningeal involvement. To explore the phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of more than one thousand CSF-DLBCs from six patients with CNSL diffuse large B-cell lymphoma (DLBCL) using Smart-seq2 single-cell RNA sequencing. CSF-DLBCs were defined based on abundant expression of B-cell markers, the active cell proliferation and energy metabolism properties, and immunoglobulin light chain restriction. We identified inherent heterogeneity of CSF-DLBCs, which were mainly manifested in cell cycle state, cancer-testis antigen expression, and classification based on single-cell germinal center B-cell signature. In addition, the 16 upregulated genes in CSF-DLBCs compared to various normal B cells showed great possibility in the homing effect of the CNS-DLBCL for the leptomeninges. Our results will provide insight into the mechanism research and diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

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The immune landscapes of primary central nervous system diffuse large B cell lymphoma

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Project description:The outcome of patients with diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) recurrence is poor. However, there is currently no consensus regarding diagnostic techniques. The aim of the present study was to investigate the cerebrospinal fluid (CSF) protein profile of DLBCL and identify a potential novel method for the early diagnosis of patients with DLBCL at high risk for subsequent CNS involvement. The CSF proteomic profiling of patients with DLBCL and a control group were compared using label-free liquid chromatography-tandem mass spectrometry. Gene Ontology and pathway analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery. The protein interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. In the present study, a total of 53 differentially expressed proteins with >1 log2 fold change (false discovery rate <0.01, P<0.05) were identified and quantified. These proteins appeared to be involved in platelet degranulation, innate immune response and cell adhesion. Two hub gene network modules were obtained by protein-protein interaction network analysis. Of these proteins, secreted protein acidic and rich in cysteine (SPARC) and proenkephalin (PENK) were significantly decreased in the CSF of patients with DLBCL, which appeared to be correlated with CNS involvement. The findings of the present study indicate that decreased expression levels of SPARC and PENK in the CSF may serve as early-phase biomarkers to evaluate the risk of CNS involvement in patients with DLBCL, enabling clinicians to offer prophylactic therapy at the time of diagnosis.

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Project description:Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B cell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a “CNS signature.” Keywords: disease state analysis

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Synchronous Cardiac and Central Nervous System Diffuse Large B-Cell Lymphoma

Project description: Not available

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Human cerebrospinal fluid autoantibody lipid microarray profiling

Project description:This SuperSeries is composed of the following subset Series: GSE37664: Human cerebrospinal fluid autoantibody lipid microarray profiling (Fig. 1A) GSE37670: Human cerebrospinal fluid autoantibody lipid microarray profiling (Fig. 2A) GSE37826: Human cerebrospinal fluid autoantibody lipid microarray profiling (Fig. 2C) Refer to individual Series

2012-05-08 | E-GEOD-37830 | biostudies-arrayexpress

Clonal evolution in diffuse large B-cell lymphoma with central nervous system recurrence.

Project description:BackgroundThe prognosis of patients with secondary central nervous system lymphoma (SCNSL) is poor and despite massive advances in understanding the mutational landscape of primary diffuse large B-cell lymphoma (DLBCL), the genetic comparison to SCNSL is still lacking. We therefore collected paired samples from six patients with DLBCL with available biopsies from a lymph node (LN) at primary diagnosis and the central nervous system (CNS) at recurrence.Patients and methodsA targeted, massively parallel sequencing approach was used to analyze 216 genes recurrently mutated in DLBCL. Healthy tissue from each patient was also sequenced in order to exclude germline mutations. The results of the primary biopsies were compared with those of the CNS recurrences to depict the genetic background of SCNSL and evaluate clonal evolution.ResultsSequencing was successful in five patients, all of whom had at least one discordant mutation that was not detected in one of their samples. Four patients had mutations that were found in the CNS but not in the primary LN. Discordant mutations were found in genes known to be important in lymphoma biology such as MYC, CARD11, EP300 and CCND3. Two patients had a Jaccard similarity coefficient below 0.5 indicating substantial genetic differences between the primary LN and the CNS recurrence.ConclusionsThis analysis gives an insight into the genetic landscape of SCNSL and confirms the results of our previous study on patients with systemic recurrence of DLBCL with evidence of substantial clonal diversification at relapse in some patients, which might be one of the mechanisms of treatment resistance.

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