Proteomic Approaches to the Discovery of Cancer Biomarkers for Early Detection and Personalized Medicine

Department of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan.
Japanese Journal of Clinical Oncology (Impact Factor: 2.02). 12/2012; 43(2). DOI: 10.1093/jjco/hys200
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Cancer biomarkers for the early detection of malignancies and selection of therapeutic strategies have been requested in the clinical field. Accurate and informative cancer biomarkers hold significant promise for improvements in the early detection of disease and in the selection of the most effective therapeutic strategies. Recently, significant progress in the comprehensive analysis of the human genome, epigenome, transcriptome, proteome and metabolome has led to revolutionary changes in the discovery of cancer biomarkers. The Human Proteome Organization has launched a global Human Proteome Project to map the entire human protein set. The Human Proteome Project research group has focused on three working proteomic pillars-mass spectrometry-based, antibody-based and knowledge-based proteomics-and each of these technologies is advancing rapidly. In this review, we introduce the proteomic platforms that are currently being used for cancer biomarker discovery, and describe examples of novel cancer biomarkers that were identified with each proteomic technology.

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    • "The experimental strategy is based on three " pillars " : mass spectrometry, antibodies, and the knowledge base, and is used to delineate the human proteome in both a chromosome-based project as well as human disease project[38]. The application of proteomics with the specified goal of developing personalized therapy has already begun in inflammatory diseases[39], cancer[40], idiopathic pulmonary fibrosis (IPF)[41], pancreatitis[31], chronic obstructive pulmonary disease (COPD)[42], acute respiratory distress syndrome[43], and asthma[44] [45], among others. "
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    ABSTRACT: Pulmonary hypertension (PH) is a fatal syndrome that arises from a multifactorial and complex background, is characterized by increased pulmonary vascular resistance and right heart afterload, and often leads to cor pulmonale. Over the past decades, remarkable progress has been made in reducing patient symptoms and delaying the progression of the disease. Unfortunately, PH remains a disease with no cure. The substantial heterogeneity of PH continues to be a major limitation to the development of newer and more efficacious therapies. New advances in our understanding of the biological pathways leading to such a complex pathogenesis will require the identification of the important proteins and protein networks that differ between a healthy lung (or right ventricle) and a remodeled lung in an individual with PH. In this article, we present the case for the increased use of proteomics-the study of proteins and protein networks- as a discovery tool for key proteins and protein networks operational in the PH lung. We review recent applications of proteomics in PH, and summarize the biological pathways identified. Finally, we attempt to presage what the future will bring with regard to proteomics in PH and offer our perspectives on the prospects of developing personalized proteomics and custom-tailored therapies.
    PROTEOMICS - CLINICAL APPLICATIONS 02/2015; 9(1-2). DOI:10.1002/prca.201400157 · 2.96 Impact Factor
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    • "The human plasma proteome is the most accessible biofluid, and has the potential to significantly improve disease diagnosis and therapeutic monitoring [32]. However, given the low abundance in serum and plasma of known cancer biomarkers [33], new proteomic technologies are constantly being developed and refined to provide sufficient depth of analysis for biomarker quantification. "
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    ABSTRACT: In the post-genomic era, it has become evident that genetic changes alone are not sufficient to understand most disease processes including pancreatic cancer. Genome sequencing has revealed a complex set of genetic alterations in pancreatic cancer such as point mutations, chromosomal losses, gene amplifications and telomere shortening that drive cancerous growth through specific signaling pathways. Proteome-based approaches are important complements to genomic data and provide crucial information of the target driver molecules and their post-translational modifications. By applying quantitative mass spectrometry, this is an alternative way to identify biomarkers for early diagnosis and personalized medicine. We review the current quantitative mass spectrometric technologies and analyses that have been developed and applied in the last decade in the context of pancreatic cancer. Examples of candidate biomarkers that have been identified from these pancreas studies include among others, asporin, CD9, CXC chemokine ligand 7, fibronectin 1, galectin-1, gelsolin, intercellular adhesion molecule 1, insulin-like growth factor binding protein 2, metalloproteinase inhibitor 1, stromal cell derived factor 4, and transforming growth factor beta-induced protein. Many of these proteins are involved in various steps in pancreatic tumor progression including cell proliferation, adhesion, migration, invasion, metastasis, immune response and angiogenesis. These new protein candidates may provide essential information for the development of protein diagnostics and targeted therapies. We further argue that new strategies must be advanced and established for the integration of proteomic, transcriptomic and genomic data, in order to enhance biomarker translation. Large scale studies with meta data processing will pave the way for novel and unexpected correlations within pancreatic cancer, that will benefit the patient, with targeted treatment.
    Journal of Translational Medicine 04/2014; 12(1):87. DOI:10.1186/1479-5876-12-87 · 3.93 Impact Factor
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    • "An improvement of the diagnostic strategy involves the possibility to detect the enzymatic activity rather than the enzyme concentration [3]. This may be especially important in cancer diagnostics and therapy where the detection of a protein is often insufficient to give information for the treatment to be used [4] [5] [6]. A clinically relevant enzyme is the human topoisomerase IB (hTop1) that represents the only target for anticancer drugs of the camptothecin (CPT) family [7]. "
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    ABSTRACT: A high sensitivity assay has been developed for the detection of human Topoisomerase I with single molecule resolution. The method uses magnetic sepharose beads to concentrate rolling circle products, produced by the amplification of DNA molecules circularized by Topoisomerase I and detectable at a confocal microscope as single and discrete dots, once reacted with fluorescent probes. Each dot, corresponding to a single cleavage-religation event mediated by the enzyme, can be counted due to its high signal/noise ratio allowing detection of 0.3 pM of enzyme and representing a valid method to detect the enzyme activity in highly diluted samples.
    Analytical Biochemistry 02/2014; 451(1). DOI:10.1016/j.ab.2014.02.003 · 2.22 Impact Factor
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