Colorectal Cancer Circulating Biomarkers

Abstract

Circulating CRC markers might become useful tools for the massive screening of people since they satisfy a high degree of accuracy, noninvasiveness, reproducibility, and economy. Within circulating biomarkers, we will focus on the detection of autoantibodies in serum from cancer patients and their target tumorassociated antigens (TAAs). Although the sensitivity, specificity, and predictive value of individual TAAs present low scores, the combination of multiple TAAs shows improved values to discriminate between CRC patients and controls. In this review, we outline the methodologies used to identify circulating autoantibodies and their target proteins and discuss the relevance of CRC autoantibodies for diagnosis at, particularly, early stages. An overview of the reported biomarkers is given, showing the large complexity of the autoantibody response in cancer. Different strategies to improve CRC diagnostic tests by combining autoantibodies from different studies will be discussed. Association of autoantibodies to prognosis, recurrence, and the survival of patients will be introduced. We conclude that there is a great potential for the use of autoantibodies as diagnostic CRC biomarkers in the near future. List of Abbreviations Key Facts of Circulating Biomarkers• Tumor-associated antigens (TAAs) are self-proteins altered during tumor formation and progression.• Cancer humoral responses take place against TAAs.• Autoantibodies against TAAs can be used in colorectal cancer patients as circulating biomarkers. • Immunoproteomics provide useful approaches for identifying autoantibodies and their reactive TAA targets.• Circulating autoantibodies provide an effective, reliable, and reproducible tool in cancer patients for diagnosis, prognosis, recurrence, and therapy monitoring.• Targets of circulating autoantibodies might be novel therapeutic targets for intervention. Definitions of Words and TermsBiomarker A biological marker usually a protein or glycoprotein that can be used as an indicator of a biological or pathological state or condition.TAA Tumor-associated antigen which consists of an altered self-protein able to induce an immune response in cancer patients.Autoantibody Immunoglobulin G produced in response to self-proteins altered during tumor formation or progression which can be used as a cancer biomarker.ELISA Enzyme-linked immunosorbent assay which permits to detect the presence of an immune response to a specific TAA in a biological fluid (i.e., serum or plasma) by means of an enzyme immunoassay.SEREX Acronym of serological analysis of recombinant cDNA expression libraries (SEREX) which is a technology based on the detection of tumor-associated antigens within recombinantly expressed tumor cDNA phage libraries by autologous antibodies.SERPA Acronym of serological proteome analysis where proteins from tumoral samples are resolved by 2D gels to identify TAAs by immunostaining with sera from cancer patients and controls. TAAs are then identified in a subsequent step by LC-MS.LC-MS Liquid chromatography ...

Development of a novel multiplex beads‐based assay for autoantibody detection for colorectal cancer diagnosis

“…Previously, we and others have used different types and versions of high-density protein microarrays (phage microarrays, glycopeptide microarrays, natural protein microarrays and recombinant ORFs protein microarrays) to character-ize the CRC humoral response [11,[19][20][21][22][23] and several CRC TAAs have been described (for reviews see [24,25]). In addition, using CRC murine models we showed that autoantibody detection allows very early CRC diagnosis providing an effective demonstration that CRC TAAs can be used for cancer screening and preclinical diagnosis [11].…”