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Quantitative Proteomics Workflow using Multiple Reaction Monitoring Based Detection of Proteins from Human Brain Tissue
Published on: August 28, 2021
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Pediatric Brain Tumors: Signatures from the Intact Proteome
Diana Valeria Rossetti1,2,3, Ilaria Inserra1, Alessia Nesticò4
1Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00185 Rome, Italy.
International Journal of Molecular Sciences
|March 25, 2022
Summary
This study analyzed pediatric brain tumor proteomes, revealing distinct molecular profiles and post-translational modifications. Findings highlight specific peptide differences in medulloblastoma and glioblastoma, offering insights into tumor progression.
Area of Science:
- Proteomics
- Oncology
- Molecular Biology
Background:
- Pediatric brain tumors exhibit diverse molecular mechanisms.
- Understanding these mechanisms is crucial for targeted therapies.
- Previous studies have focused on digested proteomes, limiting insights into intact proteins and modifications.
Purpose of the Study:
- To explore the intact proteome of pediatric brain tumors (medulloblastoma, pilocytic astrocytoma, glioblastoma) and compare with ependymoma data.
- To identify molecular differences and post-translational modifications (PTMs) associated with tumor type, grade, and localization.
- To contribute to understanding the molecular basis of pediatric brain tumor onset and progression.
Main Methods:
- Homogenization of tumor tissues in acidic solutions with protease inhibitors.
- Proteomic characterization and label-free relative quantitation using liquid chromatography-high resolution mass spectrometry (LC-HRMS).
- Top-down proteomic approach analyzing intact proteins and naturally occurring fragments.
- Bioinformatic analysis of tandem MS spectra for protein/peptide identification and PTM characterization.
- Statistical evaluation using ANOVA and Tukey's post-hoc tests.
Main Results:
- Identification of intact proteins, peptides (1.3–22.8 kDa), and biologically active fragments.
- Characterization of frequent PTMs including acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations.
- Medulloblastoma showed higher levels of thymosin β4 and β10 peptides, with specific C-terminal truncations.
- Glioblastoma exhibited distinct C-terminal truncation patterns, including gender-specific differences and a truncated α-hemoglobin chain with altered properties.
- C-terminal truncations in β-thymosin peptides and ubiquitin varied across tumor types.
Conclusions:
- The top-down proteomic approach successfully revealed PTMs and molecular profiles specific to pediatric brain tumors.
- Distinct peptide profiles and truncations in medulloblastoma and glioblastoma provide new biomarkers and therapeutic targets.
- Findings underscore the biological distinctness of male and female glioblastomas and highlight the functional significance of protein truncations.
