Biomarker discovery: tissues versus fluids versus both

DJ Johann Jr, J Blonder - Expert Review of Molecular Diagnostics, 2007 - Taylor & Francis
DJ Johann Jr, J Blonder
Expert Review of Molecular Diagnostics, 2007Taylor & Francis
Proteins are principal regulators and effectors of physiologic and pathophysiologic
processes within solitary cells, cell lines and highly complex organisms. For these reasons,
proteomics is expected to play a leading role in clinical biomarker discovery when compared
with other 'omic'-based sciences (eg, genomics and metabolomics). Importantly, only
proteomics can begin to address alternative splicing and posttranslational modifications,
which are fundamental events in complex biological processes. Unfortunately, the discovery …
Proteins are principal regulators and effectors of physiologic and pathophysiologic processes within solitary cells, cell lines and highly complex organisms. For these reasons, proteomics is expected to play a leading role in clinical biomarker discovery when compared with other ‘omic’-based sciences (eg, genomics and metabolomics). Importantly, only proteomics can begin to address alternative splicing and posttranslational modifications, which are fundamental events in complex biological processes. Unfortunately, the discovery of validated biomarkers has not kept pace with the remarkable advances in mass spectrometry (MS)-based proteomics over the past decade. To date, the translation of proteomic assays to clinically applicable diagnostic tests has been disappointing [1]. Proteomic experimental flow is complex. Routine steps include specimen selection, sample preparation, fractionation, MS analysis, data interpretation and validation. Further experimental complexity is encountered with humanbased studies due to the heterogeneity present in both clinical samples and human populations. Recently, a discussion regarding ‘tissue versus fluids’, related to the specimens of choice for protein biomarker discovery, has gained significant momentum [1]. We will discuss proteomic-based biomarker discovery approaches employed within the context of cancer. Despite a tremendous amount of scientific and clinical effort, there remains a paucity of reliable cancer biomarkers. Routine cancer screening with blood-based biomarker assays is extraordinarily difficult. Screening tests require very high values for sensitivity and (even more importantly) specificity. Currently, only serum prostate-specific antigen (PSA) is recommended as a screening test followed by patient–physician discussion of the risks and benefits of this test in the context of the patient’s age, life expectancy and likelihood of prostate cancer [2]. This fact illustrates the urgency for reliable clinical biomarkers amenable to early cancer detection.
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