Dataset Information

Design and development of nanoproteomics strategies for biomarker identification in cerebrospinal fluid of leptomeningeal disease, using as model lymphoma non-Hodgkin B.

ABSTRACT: The early diagnosis of leptomeningeal disease is a challenge because it is an asymptomatic pathology in the early stages. Hence, it is highly relevant to identify a panel of biomarkers to help in the diagnosis and/or prognostic. For this purpose, we have explored a multipronged proteomics approaches, in cerebrospinal fluid, to determine a potential panel of biomarkers in cerebrospinal fluid. Thus, a systematic and exhaustive characterization of more than 347 CSF samples have been performed by an integrated LC-MS/MS (n 20) and functional proteomics (n 347) analysis to establish protein profiles which has been useful to develop a panel of biomarkers validated by in silico approaches.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Pablo Juanes-Velasco

LAB HEAD: Manuel Fuentes García

PROVIDER: PXD026016 | Pride | 2022-02-17

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 300

Publications

Deciphering Biomarkers for Leptomeningeal Metastasis in Malignant Hemopathies (Lymphoma/Leukemia) Patients by Comprehensive Multipronged Proteomics Characterization of Cerebrospinal Fluid.

Juanes-Velasco Pablo P Galicia Norma N Pin Elisa E Jara-Acevedo Ricardo R Carabias-Sánchez Javier J García-Valiente Rodrigo R Lecrevisse Quentin Q Pedreira Carlos Eduardo CE Gongora Rafael R Sanchez-Santos Jose Manuel JM Lorenzo-Gil Héctor H Landeira-Viñuela Alicia A Bareke Halin H Orfao Alberto A Nilsson Peter P Fuentes Manuel M

Cancers 20220117 2

In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in ...[more]

PMID: 35053611

Similar Datasets

Project description:Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS). However it remains unresolved whether autologous CD34+ hematopoietic progenitor cells of MS patients show gene expression differences prior to aHSCT that indicate a preset proinflammatory state, which would then also predispose to or predetermine recurrence of the autoimmune disease. To approach this key point we compared the gene expression signature of CD34+ and CD34- cells collected from MS patients and healthy donors (HD). Whole genome gene expression of CD34+ and CD34- cells was analysed with the Human 4x44K Design Array (Agilent-Technologies). As main observation we found only minor differences in the gene expression signature of MS patients compared to HD. Only a single gene, troponin-type-1 (TNNT1), reached statistical significance after correction for multiple comparisons (logFC=3.1, p<0.01). There was a decreased expression of several protease genes, myeloperoxidase (MPO), neutrophil-elastase (ELA2), cathepsin-G (CTSG) and serine-protease 21 (PRSS21) in HPCs of MS patients, albeit not reaching statistical significance. In summary we did not detect substantial alterations in the gene expression profile of CD34+ HPCs in MS. Our data support the use of autologous hematopoietic stem cell transplantation for treatment of an autoimmune disease. Samples of CD34+ cells were obtained from 4 female MS patients and 4 age matched healthy donors (3 female) mobilized by G-CSF (2x5M-NM-<g/kg/day) and 4 MS patients (2 female) mobilized by G-CSF (5M-NM-<g/kg/day) plus Cyclophosphamide (Cy, 4g/m2). White blood cells, containing the CD34+ cell fraction, were collected by leucocytapheresis from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and processed at one center and CD34+ HPCs purified by magnetic bead separation using the autoMACS system (Miltenyi). Purity and viability of CD34+ cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human 4x44K Design Array (Agilent-Technologies).

Project description:Background. COVID-19-induced neurological disease is a growing concern. Here we provide a comprehensive clinical, molecular, and neuroimaging investigation of patients presenting neurological symptoms to investigate underlying processes. Methods. We performed a detailed systematized clinical, laboratory, and neuroimaging (CT/MRI) data analysis from 35 mild to severe Brazilian COVID-19 hospitalised patients with clinical indications for cerebrospinal fluid (CSF) exam. In patients' CSF, we measured interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and the Alzheimer's disease-associated biomarkers amyloid-beta (Aβ)1-40, Aβ1-42, Tau and pTau181 levels (n=31-35). In addition, CSF proteomics and the search for SARS-CoV-2 spike protein presence using shotgun and targeted multiple reaction monitoring liquid-chromatography/mass-spectrometry were performed (n=16). We further evaluated a 29-cytokine panel in patients’ blood (n=16). An electronic questionnaire was conducted one-year post-hospitalisation (n=19, 63.3%). Findings. COVID-19 patients presented heterogeneous clinical and neurological features, including encephalopathy, encephalitis, and neuromuscular syndromes, despite low pulmonary burden. Patients showed increased circulating cytokines and CSF IL-6 and TNF-α levels compared to controls. Alzheimer’s disease-related biomarkers were unaltered compared to controls. COVID-19 altered CSF proteomic pathways associated to complement and coagulation cascades, immune-inflammatory, metabolism and amyloidosis. We found no traces of spike protein in patients’ CSF. Severe patients presented more pronounced neuroimaging alterations, altered CSF levels of IL-6, Tau, and Aβ-species compared to mild patients. Peripheral inflammation markers correlated with CSF IL-6 and Tau-species levels. Finally, in a one-year post-COVID survey, survivors were not recovered entirely (12/19) and reported confusion or memory/attention deficits (13/19). Interpretation. COVID-19 induces a broad spectrum of neurological presentations associated with changes in central nervous system (CNS) inflammatory and neurodegenerative molecular and structural biomarkers that correlate with systemic inflammation and disease severity. Given that neurological symptoms persist up to one-year post-COVID, our results urge us to investigate whether systemic, and CNS molecular changes are permanent or alleviated so that COVID-19 patients with lingering symptoms are adequately treated.

			Action	DRS
	0203_10_1.mgf	Mgf
	0203_10_1.msf	Msf
	0203_10_1.mzid.gz	Mzid
	0203_10_1.raw	Raw
	0203_10_1_Protocol.txt	Txt