Abstract
Mass spectrometry-based analyses of the low-molecular-weight fraction of serum proteome allow identifying proteome profiles (signatures) that are potentially useful in detection and classification of cancer. Several published studies have shown that multipeptide signatures selected in numerical tests have potential values for diagnostics of different types of cancer. However due to apparent problems with standardization of methodological details, both experimental and computational, none of the proposed peptide signatures analyzed directly by MALDI/SELDI-ToF spectrometry has been approved for routine diagnostics. Noteworthy, several components of proposed cancer signatures, especially those characteristic for advanced cancer, were identified as fragments of blood proteins involved in the acute phase and inflammatory response. This indicated that among cancer biomarker candidates to be possibly identified by serum proteome profiling were rather those reflecting overall influence of a disease (and the therapy) upon the human organism, than products of cancer-specific genes. Current paper focuses on changes in serum proteome that are related to response of patient's organism to progressing malignancy and toxicity of anticancer treatment. In addition, several methodological issues that affect robustness and interlaboratory reproducibility of MS-based serum proteome profiling are discussed.
Highlights
Cancer Markers and Clinical ProteomicsBiological factors (e.g., proteins), whose status and/or quantity reflect the risk of a disease, severity of an illness, or the effects of therapy are called markers or biomarkers
Due to apparent problems with standardization of methodological details, both experimental and computational, none of the proposed peptide signatures analyzed directly by matrix-assistedlaser(induced)desorption ionization (MALDI)/surface-enhanced laser desorption ionization (SELDI)-time of flight (ToF) spectrometry has been approved for routine diagnostics
Several protein tumor markers have been used for decades in the traditional oncology for detection of cancer, for example, prostate cancer antigen (PSA) or cancer antigen 125 kD (CA125)
Summary
Biological factors (e.g., proteins), whose status and/or quantity reflect the risk of a disease, severity of an illness, or the effects of therapy are called markers or biomarkers. MALDI/SELDI-based profiling of the low-molecular-weight fraction of serum/plasma proteome for cancer diagnostics since the milestone paper was published by Petricoin and coworkers in 2002 [19] These studies have shown that multipeptide signatures selected in numerical tests have potential values for diagnostics of different types of cancer. Several components of proposed cancer signatures, especially those for advanced cancer, were identified as fragments of blood proteins involved in the acute phase and inflammatory response [34, 48, 54] This indicated that among cancer biomarker candidates to be possibly identified in serum proteome were rather those reflecting overall influence of a disease (and the therapy) upon the human organism, than cancer-specific molecules. We aimed to point out the methodological issues that affect robustness of MS-based serum proteome profiling and to focus on two particular areas where such analyses seem to be the most rational and promising: assessment of cancer progression and monitoring of cancer treatment
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