TY - JOUR
T1 - Deciphering Biomarkers for Leptomeningeal Metastasis in Malignant Hemopathies (Lymphoma/Leukemia) Patients by Comprehensive Multipronged Proteomics Characterization of Cerebrospinal Fluid
AU - Juanes-Velasco, Pablo
AU - Galicia, Norma
AU - Pin, Elisa
AU - Jara-Acevedo, Ricardo
AU - Carabias-Sánchez, Javier
AU - García-Valiente, Rodrigo
AU - Lecrevisse, Quentin
AU - Pedreira, Carlos Eduardo
AU - Gongora, Rafael
AU - Sanchez-Santos, Jose Manuel
AU - Lorenzo-Gil, H. ctor
AU - Landeira-Viñuela, Alicia
AU - Bareke, Halin
AU - Orfao, Alberto
AU - Nilsson, Peter
AU - Fuentes, Manuel
N1 - Funding Information:
We gratefully acknowledge financial support from the Spanish Health Institute, Carlos III (ISCIII), for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID-19 grant COV20EDU/00187). The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D + I 2017-2020, funded by ISCIII and FEDER—Norma Galicia is supported by the CONACYT Program. P. Juanes-Velasco is supported by JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYL-EDU/601/2020.
Funding Information:
Acknowledgments: We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID19 grant COV20EDU/00187). Fundación Solórzano FS/38-2017. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. Luis Romero Martín for technical support in microarray processing. P. Juanes-Velasco is supported by JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYL-EDU/601/2020.
Funding Information:
Funding: We gratefully acknowledge financial support from the Spanish Health Institute, Carlos III (ISCIII), for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID-19 grant COV20EDU/00187). The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D + I 2017-2020, funded by ISCIII and FEDER—Norma Galicia is supported by the CONACYT Program. P. Juanes-Velasco is supported by JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYL-EDU/601/2020.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - CSF-stabilizing reagents
KW - Cerebrospinal fluid (CSF)
KW - High-abundant protein depletion
KW - LC-MS/MS
KW - Leptomeningeal metastasis (LM)
KW - Modelling leptomeningeal disease
KW - Protein microarrays
KW - Protein-based biomarker
KW - Proteomic analysis
KW - Tumor infiltrating
UR - https://www.scopus.com/pages/publications/85122882643
U2 - 10.3390/cancers14020449
DO - 10.3390/cancers14020449
M3 - Article
C2 - 35053611
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 2
M1 - 449
ER -
SDG 3 Good Health and Well-being