Application of MALDI/SELDI Mass Spectrometry to Cancer Biomarker Discovery and Validation

Abstract

This article provides a focused perspective on the application of MALDI/SELDI mass spectrometry (MS)-based technologies to biomarker discovery and validation in various biological materials, which might eventually serve as the basis for new clinical tests to improve diagnosis, guide molecularly-targeted therapy, and monitor the activity and therapeutic response to various cancers. However, the contribution of MALDI/SELDI MS to these goals has been scant due partially to current unavailability of robust analytical methods and instruments to overcome the finite complexity of the proteome and peptidome. Moreover, with a coherent pipeline, the successful throughput from marker discovery to robust validation methods has been dismal. While the development of a faster and more sensitive MS methods will have a major impact on the ability to identify thousands of proteins in body fluids, improvement in sample preparation methods such as high abundance protein depletion and chromatography, and better sample processing methods have also played key roles. Further optimization of MS-based methods is expected to further improve their analytical performance. Because of the guarded skepticism voiced by several investigators about the ultimate value of the entire MS-based proteomics approach for biomarker discovery in complicated samples such as blood, exhaustive experimental methods that use multiple reaction monitoring targeted proteomic approaches, which include immunoassays coupled with MS spectrometry techniques need to be developed and standardized, initially for less complex body fluids, tissues, or even cells or tissue explants in animal models and later on translated to blood, in order to avoid the pitfalls of bias and/or overfitting that plagued earlier studies, and it is still hoped that eventually proteomic profiling in complex biological samples will become a fulfilled promise rather than just an unrealized hope for the scientific and clinical community.

Selective enrichment and sensitive detection of peptide and proteinbiomarkers in human serum using polymeric reverse micelles and MALDI-MS

“…MALDI-MS approaches do not usually detect as many different peptides and proteins as LC/ESI-MS methods, but they do provide nice advantages with regard to small sample sizes and high throughput when combined with specialized affinity enrichment/fractionation techniques such as surface enhanced laser desorption ionization (SELDI) chips. 11–16 Indeed, MALDI-MS has become a powerful approach for screening novel disease-related biomarkers. 17–22 …”

Sample preparation and fractionation for proteome analysis and cancer biomarker discovery by mass spectrometry

“…Application of SELDI technology and the generated proteomic patterns for the analysis of differences in proteins between healthy and cancer-bearing individuals has raised many concerns due to various discrepancies, as illustrated in the body of this review, in a recent review on the subject [230] and in Table 5 [231,232]. MALDI profiling, although has given better results than SELDI, still needs further standardization and evaluation [233].…”

“…MALDI profiling, although has given better results than SELDI, still needs further standardization and evaluation [233]. Although, a recently developed carrier-based approach called MELDI is an improvement on the MALDI approach, and appears to enhance the robustness and throughput of large-scale proteomic studies [234,235], neverthless, it still needs confirmation [230].…”

A time series approach for clustering mass spectrometry data

“…Two of the earliest techniques for generating mass spectra are Matrix-Assisted Laser Desorption/Ionization -Time Of Flight Mass Spectrometry (MALDI-TOF MS) [2] and Surface-Enhanced Laser Desorption/Ionization -Time Of Flight Mass Spectrometry (SELDI-TOF MS) [3]. Although MALDI-TOF and SELDI-TOF have been widely used with success for years [4], a number of novel techniques for MS generation have been developed recently, such as Liquid Chromatography ElectroSpray Ionisation Mass Spectrometry (LC-ESI MS) [5] or Capillary Electrophoresis Mass Spectrometry (CE MS) [6].…”