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

• Published in: Cancers Vol. 14; no. 2; p. 449
• Main Authors: Juanes-Velasco, Pablo, Galicia, Norma, Pin, Elisa, Jara-Acevedo, Ricardo, Carabias-Sánchez, Javier, García-Valiente, Rodrigo, Lecrevisse, Quentin, Pedreira, Carlos Eduardo, Gongora, Rafael, Sanchez-Santos, Jose Manuel, Lorenzo-Gil, Héctor, Landeira-Viñuela, Alicia, Bareke, Halin, Orfao, Alberto, Nilsson, Peter, Fuentes, Manuel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17-01-2022; MDPI
• Subjects: Biomarkers; Blood; Brain cancer; Brain research; Cellular biology; Central nervous system; Cerebrospinal fluid; cerebrospinal fluid (CSF); CSF-stabilizing reagents; Diagnosis; Disease; Fc receptors; Fluids; high-abundant protein depletion; LC-MS; leptomeningeal metastasis (LM); Leukemia; Life span; Liquid chromatography; Lymphoma; Mass spectroscopy; Medical prognosis; Medical research; Meninges; Meningitis; Metastases; Metastasis; modelling leptomeningeal disease; Nervous system; Pathology; Prediction models; Prognosis; protein microarrays; protein-based biomarker; Proteins; proteomic analysis; Proteomics; Tumor cells; tumor infiltrating; Tumors; United States > US; CSF-stabilizing reagents; leptomeningeal metastasis (LM); LC-MS/MS; tumor infiltrating; cerebrospinal fluid (CSF); high-abundant protein depletion; modelling leptomeningeal disease; biomarkers; protein-based biomarker; protein microarrays; proteomic analysis
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14020449

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.