Cerebrospinal fluid top-down proteomics evidenced the potential biomarker role of LVV- and VV-hemorphin-7 in posterior cranial fossa pediatric brain tumors
Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Rome, Italy.Proteomics (Impact Factor: 3.81). 07/2012; 12(13):2158-66. DOI: 10.1002/pmic.201100499
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: Background Adamantinomatous craniopharyngioma is the third most recurrent paediatric brain tumour. Although histologically benign, it behaves aggressively as a malignant tumour due to invasion of the hypothalamus and visual pathways. Surgery is still the first and almost the only mode of treatment, although serious damage can occur as a consequence of tumour localization. The proteomic characterization of the intracystic tumoural fluid could contribute to the comprehension of the tumorigenesis processes and to the development of therapeutic targets to reduce cyst volume, allowing less invasive surgery and/or delay of the radical resection of the tumour mass and the collateral serious effects. Methods Intracystic fluid was analysed by a LC-ESI-IT-MS top-down platform after acidification, deproteinization and chloroform liquid/liquid extraction. Findings Thymosin β4 and β10 peptides were for the first time identified in the intracystic fluid of adamantinomatous craniopharyngioma by low- and high-resolution MS analysis coupled with LC. The two peptides showed the same distribution trend in the analysed samples. Thymosin β4 and β10 were present in 77 % of the analysed samples. These peptides were not found in the cerebrospinal fluid available for two patients. Interpretation The presence of β-thymosins in the intracystic fluid of the tumour confirmed the secretion of these proteins in the extracellular environment. Due to their G-actin-sequestering activity and antiapoptotic and anti-inflammatory properties, these peptides could be strictly involved in both tumour progression and cyst development and growth.Child s Nervous System 06/2013; 29(6). DOI:10.1007/s00381-013-2069-9 · 1.11 Impact Factor
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ABSTRACT: Posttranslational modifications (PTMs) are dynamic regulators of protein function, and play important roles in diseases such as cancer. PTM analysis can be challenging, the stoichiometry of PTMs is often low, and various combinatorial modifications are possible. Currently, two major techniques are used to detect and characterize PTMs, immunoassays and mass spectrometry. Immunoassays rely on antibodies for detection of the protein of interest, and are therefore limited to targeted analysis. Mass spectrometry, on the other hand, is capable of characterizing posttranslational modifications both in targeted or non-targeted methods. Recently, new immunoassays were introduced that improve current methods, but also appear particularly promising in the analysis of PTMs. Two of these new immunoassays, proximity ligation assay and nanoscale immunoassay, are discussed in this review. In contrast to immunoassays, mass spectrometry enables characterization of a priori unknown PTM sites. A bottom-up approach, in which proteins are digested into smaller peptides, is well suited for targeted assays as well as cataloging PTMs. A top-down approach, where intact proteins are measured, is challenging but allows mapping of combinatorial PTMs. Mass spectrometry and immunoassays are therefore complementary techniques in analysis of PTMs. Advances in these methods now enable extremely sensitive detection of PTMs from very little material (immunoassays), or can fully characterize combinatorial modifications on proteins in both targeted and non-targeted ways (mass spectrometry). Recent developments in these techniques discussed in this review will therefore likely play an important role in current and future PTM analysis, particularly in the field of cancer research.Current Proteomics 08/2013; 10:98-119. DOI:10.2174/1570164611310020004 · 0.64 Impact Factor
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ABSTRACT: Mass spectrometry (MS)-based proteomics is a rapidly developing technology for the large scale analysis of proteins, their interactions and subcellular localization. In recent years proteomics has attracted much attention in medicine. Since a single biomarker might not have sufficient sensitivity and specificity in clinical practice, the identification of biomarker panels that comprise several proteins would improve the detection and clinical management of cancer patients. Additionally, the characteristics of protein profiles of most severe human malignancies certainly contribute to the understanding of the biology of cancer and fill the gap in our knowledge of carcinogenesis. This knowledge also is likely to result in the discovery of novel potential cancer markers and targets for molecular therapeutics. It is believed that the novel biomarkers will help in the development of personalized therapy tailored to the individual patient and will thereby reduce the mortality rate from cancer. In this review, the use of different types of human clinical samples (cell cultures, tissues and body fluids) in oncoproteomics is explained and the latest advances in mass spectrometry-based proteomics biomarker discovery are discussed.Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 01/2014; 68:1312-24. DOI:10.5604/17322693.1129117 · 0.57 Impact Factor
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