Blood-Based Protein Signatures for Early Detection of Colorectal Cancer: A Systematic Review.

OBJECTIVES: Blood-based proteins might be an attractive option for early detection of colorectal cancer (CRC), but individually they are unlikely to achieve the diagnostic performance required for population based screening. We aimed at summarizing current evidence of diagnostic performance of signatures based on multiple proteins for early detection of CRC.

METHODS: A systematic literature review adhering to the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines was performed. PubMed and Web of Science databases were searched for potentially relevant studies published until 28th August, 2017. Relevant studies were identified by predefined eligibility criteria. Estimates of indicators of diagnostic performance such as sensitivity, specificity, and the area under the curve (AUC), along with information on validation and other key methodological procedures were extracted. Study quality was assessed by a QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) instrument tool.

RESULTS: Thirty six eligible studies with numbers of CRC cases ranging from 23 to 512 and the number of proteins included in signatures ranged from 3 to 13 were identified. Reported Youden's Index and AUC ranged from 0.19 to 0.95 and from 0.62 to 0.996, respectively. However most studies, especially those reporting better diagnostic performance, were conducted in clinical rather than screening setting and many studies lacked any internal or external validation of identified algorithm.

CONCLUSIONS: Blood-based tests using signatures of multiple proteins may be a promising approach for non-invasive CRC screening. However, promising signatures identified in clinical settings still require rigorous evaluation in large studies conducted in true screening setting.