Protein Profiling in Brain Tumors Using Mass Spectrometry

Abstract

Purpose: The purpose of this research was to perform a preliminary assessment of protein patterns in primary brain tumors using a direct-tissue mass spectrometric technique to profile and map biomolecules.Experimental Design: We examined 20 prospectively collected, snap-frozen normal brain and brain tumor specimens using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS), and compared peptide and protein expression in primary brain tumor and nontumor brain tissues.Results: MS can be used to identify protein expression patterns in human brain tissue and tumor specimens. The mass spectral patterns can reliably identify glial neoplasms of similar histological grade and differentiate them from tumors of different histological grades as well as from nontumor brain tissues. Initial bioinformatics cluster analysis algorithms classified tumor and nontumor tissues into similar groups comparable with their histological grade.Conclusions: We describe a novel tool for the analysis of protein expression patterns in human glial neoplasms. Initial results demonstrate that MALDI-MS technology can significantly aid in the process of unraveling and understanding the molecular complexities of gliomas. MALDI-MS accurately and reliably identified normal and neoplastic tissues, and could be used to discriminate between tumors of increasing grades.

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

“…This could take us one step closer to the ultimate possibility of individualising treatment modalities and monitoring the effects instantly, especially with regard to all of the novel drugs that now are introduced in the clinic (Krause and Van Etten, 2005). The use of protein expression profiling may also be important in neuro-oncology for the subclassification of tumours (Furuta et al, 2004;Schwartz et al, 2004;Liu et al, 2005), as a complementary approach to the morphological and genomic methods currently used (Kleihues and Ohgaki, 1997).…”

“…In malignant glioma it is possible to distinguish between tumour and nonmalignant brain tissue, as well as between different grades of glioma, using direct-tissue analysis by matrix-assisted laser desorption/ionisation (MALDI) MS and subsequent cluster analysis (Schwartz et al, 2004). To date, however, the main focus of studies employing proteomics has been to detect biological markers for early diagnosis of disease.…”

The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: evidence from mass spectrometry profiling

“…Since the concept of directly identifying molecules on tissues using MALDI ion sources was proposed at the end of the 1990s (Caprioli et al 1997), MALDI imaging mass spectrometry has been used in many clinical applications (Cornett et al 2006;El Ayed et al 2010;Lemaire et al 2006a, b;Pevsner et al 2009;Schwamborn et al 2007;Schwartz et al 2004;Seeley and Caprioli 2008). A decade of developments in instrumentation and chemistry has been required to achieve optimal extraction, detection, and spatial resolution when mapping compounds at the tissue level (Franck et al 2009a, b;Lemaire et al 2006a, b;2007a;van Remoortere et al 2010).…”

Proteomics in pathology research

“…[39][40][41][42][43][44] Imaging Mass Spectrometry Mass spectrometry has been used for the in situ analyses of proteins in tissue sections and those obtained by laser capture microdissection, 53 thereby allowing imaging and comparison of protein expression between normal and disease tissues. [54][55][56][57][58][59][60][61] In this strategy, frozen tissue sections are applied to a MALDI plate and analyzed at regular spatial intervals. The mass spectral data obtained at different intervals are compared to yield a spatial distribution of masses (proteins) across the tissue section.…”