Cerebrospinal fluid top-down proteomics evidenced the potential biomarker role of LVV- and VV-hemorphin-7 in posterior cranial fossa pediatric brain tumors.
ABSTRACT Posterior cranial fossa is the most frequent location of pediatric brain tumors. Its diagnosis is currently performed by postsurgery histopathology and the identification of biomarkers in cerebrospinal fluid (CSF) could provide a less invasive tool. Patient CSF was collected during surgery before the tumor removal (PRE-CSF) and 6 days after the resection (POST-CSF) and analyzed by top down LC-MS proteomics for comparison. The PRE-CSFs generally exhibited a less complex LC-MS profile than the relative POST-CSFs suggesting a suppressive role of the tumor toward proteins and peptides production or release. Particularly, a panel of peptides, identified as alpha- and beta-hemoglobin chains fragments, were generally absent in the PRE-CSF and present in the POST ones independently from contaminant blood hemoglobin. Among them, the LVV- and VV-hemorphin-7 showed the most repeatable trend and with a few remarkable exceptions: their unusual absence in POST surgery CSF was in fact interestingly correlated to the presence of tumor in the patient despite surgery due to metastases or to subtotal resection. These results ascribed a relevant biological role to LVV- and VV-h7 peptides in the disease and a strong potential as biomarkers. Their analysis in POST surgery CSF could be used to predict patient prognosis.
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ABSTRACT: Proteomics is essential for deciphering how molecules interact as a system and for understanding the functions of cellular systems in human disease; however, the unique characteristics of the human proteome, which include a high dynamic range of protein expression and extreme complexity due to a plethora of post-translational modifications (PTMs) and sequence variations, make such analyses challenging. An emerging “top-down” mass spectrometry (MS)-based proteomics approach, which provides a “bird's eye” view of all proteoforms, has unique advantages for the assessment of PTMs and sequence variations. Recently, a number of studies have showcased the potential of top-down proteomics for unraveling of disease mechanisms and discovery of new biomarkers. Nevertheless, the top-down approach still faces significant challenges in terms of protein solubility, separation, and the detection of large intact proteins, as well as the under-developed data analysis tools. Consequently, new technological developments are urgently needed to advance the field of top-down proteomics. Herein, we intend to provide an overview of the recent applications of top-down proteomics in biomedical research. Moreover, we will outline the challenges and opportunities facing top-down proteomics strategies aimed at understanding and diagnosing human diseases.This article is protected by copyright. All rights reservedProteomics 04/2014; · 4.43 Impact Factor
- Current Proteomics 01/2013; 10:98-119. · 0.83 Impact Factor
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ABSTRACT: Primary brain tumors cumulatively represent the most common solid tumors of childhood and are the leading cause of cancer related death in this age group. Traditionally, molecular findings and histological analyses from biopsies of resected tumor tissue have been used for diagnosis and classification of these diseases. However, there is a dearth of useful biomarkers that have been validated and clinically implemented for pediatric brain tumors. Notably, diseases of the central nervous system (CNS) can be assayed through analysis of cerebrospinal fluid (CSF) and as such, CSF represents an appropriate medium to obtain liquid biopsies that can be informative for diagnosis, disease classification and risk stratification. Proteomic profiling of pediatric CNS malignancies has identified putative protein markers of disease, yet few effective biomarkers have been clinically validated or implemented. Advances in protein quantification techniques have made it possible to conduct such investigations rapidly and accurately through proteome-wide analyses. This review summarizes the current literature on proteomics in pediatric neuro-oncology and discusses the implications for clinical applications of proteomics research. We also outline strategies for translating effective CSF proteomic studies into clinical applications to optimize the care of this patient population.Journal of Neuro-Oncology 04/2014; · 3.12 Impact Factor