Finding Needles in Haystacks: The Use of Quantitative Proteomics for the Early Detection of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is a common and treatable disease if diagnosed early. Current population screening programs are suboptimal, and consequently, there is a need for the development of new methodologies for early diagnosis of CRC. In the past 10 years, unprecedented technological advancements in the field of mass spectrometry (MS)-based proteomics have progressively increased the sophistication and utility of these investigations, leading to the draft mapping of the human proteome. These exciting studies have shaped our mechanistic understanding of the human genome and begun to provide us with a suite of novel biomarkers to predict the onset, progression and severity of many debilitating diseases. Thus, sophisticated MS workflows coupled with revolutionary protein quantification techniques hold promise for the field of MS-based plasma proteomics, particularly valuable in the context of early stage identification of curable CRC. However, within the last 40 years, no new plasma protein biomarkers of CRC have been translated into clinical practice. Here. we discuss the application of proteomic technologies within the field of CRC, highlighting contemporary MS-based plasma proteomic strategies that could be exploited to deliver on the promise of a panel of sensitive and specific plasma-based biomarkers with which to non-invasively detect early stage CRC.

Carbon-Based Nanomaterials as Drug Delivery Agents for Colorectal Cancer: Clinical Preface to Colorectal Cancer Citing Their Markers and Existing Theranostic Approaches

“…With regard to serum biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 are established, well-studied, and extensively used. Other serum proteins like apolipoproteins, cystatins, haptoglobin, serum amyloid A, C-reactive protein (CRP), alpha1-antitrypsin (AAT), preoperative transferrin, β-2 microglobulin, heat shock proteins (HSP27, HSP40, HSP60, HSP70, HSP90A, and HSP110), matrix metalloproteinases (MMP-1, -2, -3, -7, -9, -12 and -13), complement components C3 and C9, macrophage mannose receptor 1 (MRC1), S100A9, paraoxonase 1, human neutrophil peptides, uromodulin, gelsolin, meprin 1α (MEP1A), α-enolase, and transthyretin can serve as predictive markers for CRC. − Mutations of KRAS , BRAF , NRAS , PIK3CA , APC , TP53 , SMAD4 , NF1 , ARID1A , SOX9 , and FAM123B remain significant as genomic markers. − …”