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Targeted proteomics for biomarker discovery and validation of hepatocellular carcinoma in hepatitis C infected patients

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World Journal of Hepatology 2015年第10期7卷 1312-1324页

作者： Gul M Mustafa denner larry John R Petersen Cornelis J Elferink Department of Pharmacology and Toxicology University of Texas Medical Branch Department of Internal Medicine University of Texas Medical Branch Department of Pathology School of Medicine University of Texas Medical Branch

Hepatocellular carcinoma(HCC)-related mortality is high because early detection modalities are hampered by inaccuracy,expense and inherent procedural *** there is an urgent need for minimally invasive,highly specific and sensitive biomarkers that enable earlydisease detection when therapeutic intervention remains practical. Successful therapeutic intervention is predicated on the ability to detect the cancer early. Similar unmet medical needs abound in most fields of medicine and require novel methodological approaches. Proteomic profiling of body fluids presents a sensitive diagnostic tool for early cancer detection. Here we describe such a strategy of comparative proteomics to identify potential serum-based biomarkers to distinguish high-risk chronic hepatitis C virus infected patients from HCC patients. In order to compensate for the extraordinary dynamic range in serum proteins,enrichment methods that compress the dynamic range without surrendering proteome complexity can help minimize the problems associated with many depletion methods. The enriched serum can be resolved using 2D-difference in-gel electrophoresis and the spots showing statistically significant changes selected for identification by liquid chromatographytandem mass spectrometry. Subsequent quantitative verification and validation of these candidate biomarkers represent an obligatory and rate-limiting process that is greatly enabled by selected reaction monitoring(SRM). SRM is a tandem mass spectrometry method suitable for identification and quantitation of target peptides within complex mixtures independent on peptidespecific antibodies. Ultimately,multiplexed SRM and dynamic multiple reaction monitoring can be utilized for the simultaneous analysis of a biomarker panel derived from support vector machine learning approaches,which allows monitoring a specific disease state such as early HCC. Overall,this approach yields high probability biomarkers for clinical validation in large patient

关键词： Hepatocellular carcinoma Biomarkers Early detection Selected reaction monitoring Targetedproteomics

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