Abstract
Searching for new cancer-related biomarkers is a key priority for the early detection of solid tumors, such as colorectal cancer (CRC), in clinically relevant biological fluids. The cell line and/or tumor tissue secretome represents a valuable resource for discovering novel protein markers secreted by cancer cells. The advantage of a secretome analysis is the reduction of the large dynamic range characterizing human plasma/serum, and the simultaneous enrichment of low abundance cancer-secreted proteins, thereby overcoming the technical limitations underlying the direct search in blood samples. In this review, we provided a comprehensive overview of recent studies on the CRC secretome for biomarker discovery, focusing both on methodological and technical aspects of secretome proteomic approaches and on biomarker-independent validation in CRC patient samples (blood and tissues). Secretome proteomics are mainly based on LC-MS/MS analyses for which secretome samples are either in-gel or in-solution trypsin-digested. Adequate numbers of biological and technical replicates are required to ensure high reproducibility and robustness of the secretome studies. Moreover, another major challenge is the accuracy of proteomic quantitative analysis performed by label-free or labeling methods. The analysis of differentially expressed proteins in the CRC secretome by using bioinformatic tools allowed the identification of potential biomarkers for early CRC detection. In this scenario, this review may help to follow-up the recent secretome studies in order to select promising circulating biomarkers to be validated in larger screenings, thereby contributing toward a complete translation in clinical practice.
Highlights
Detection through specific molecular markers is still a key step affecting the clinical management of cancer
Given that the cancer secretome is a reservoir of tumor-associated antigens (TAAs), affinity strategy coupled to MS-based proteomics could be a promising approach for capturing immunogenic biomarkers directly from sera of colorectal cancer (CRC) patients, but its intrinsic limit is related to the specificity of the antibody development
We previously reported the secretome signatures of two CRC cell lines (CaCo-2 and HCT-GEO), and among the identified proteins, more than a half were classified as secretory by in silico analysis [34]
Summary
Detection through specific molecular markers is still a key step affecting the clinical management of cancer. The main drawbacks are related to the heterogeneity of the biological matrix and its very high dynamic range of concentrations among species (up to 12 orders of magnitude in plasma/serum): such a complexity represents a challenging task (depletion of highly concentrated species, sample pooling) when trying to reliably detect low abundance cancer-related biomarkers [10,11,12,13,14,15,16,17] These experimental limits, along with the difficulties of translating the results into clinical applications, have discouraged researchers from following that path [11]. The emerging data from the most recent publications are overviewed to point out the potential of secretome analysis for the identification of new circulating biomarker candidates
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