Deciphering biomarkers for leptomeningeal metastasis in malignant hemopathies (Lymphoma/Leukemia) patients by comprehensive multipronged proteomics characterization of cerebrospinal fluid

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 cerebrosp...

Descripción completa

Detalles Bibliográficos
Autores: Juanes-Velasco, Pablo, Galicia, N., Pin, Elisa, Jara-Acevedo, Ricardo, Carabias-Sánchez, Javier, García-Valiente, R., Lécrevisse, Quentin, Pedreira, C. E., Góngora, Rafael, Sánchez-Santos, José Manuel, Lorenzo-Gil, Héctor, Landeira-Viñuela, Alicia, Bareke, Halin, Orfao, Alberto, Nilsson, Peter, Fuentes, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/286177
Acceso en línea:http://hdl.handle.net/10261/286177
Access Level:acceso abierto
Palabra clave:cerebrospinal fluid (CSF)
Leptomeningeal metastasis (LM)
Biomarkers
High-abundant protein depletion
CSF-stabilizing reagents
Tumor infiltrating
Modelling leptomeningeal disease
Proteomic analysis
LC-MS/MS
Protein microarrays
Protein-based biomarker
Descripción
Sumario: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 most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease.