Multiplex quantitation of 270 plasma protein markers to identify a signature for early detection of colorectal cancer. (March 2020)

• Record Type: Journal Article
• Authors: Bhardwaj, Megha; Weigl, Korbinian; Tikk, Kaja; Holland-Letz, Tim; Schrotz-King, Petra; Borchers, Christoph H.; Brenner, Hermann
• Is Part Of: European journal of cancer. Volume 127(2020)
• Page Start: 30
• Page End: 40
• Publication Date: 2020-03
• Subjects: Colorectal cancer -- Early detection -- Cancer prevention -- Cancer biomarkers -- Prevention and screening -- Proteomics -- Sensitivity -- Specificity; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2019.11.021
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Blood-based protein biomarker signatures might be an alternative or supplement to existing methods for early detection of colorectal cancer (CRC) for population-based screening. The objective of this study was to derive a protein biomarker signature for early detection of CRC and its precursor advanced adenoma (AA). In a two-stage design, 270 protein markers were measured by liquid chromatography/multiple reaction monitoring/mass spectrometry in plasma samples of discovery and validation sets. In the discovery set consisting of 100 newly diagnosed CRC cases and 100 age- and sex-matched controls free of neoplasm at screening colonoscopy, the algorithms predicting the presence of early- or late-stage CRC were derived by Lasso regression and .632 + bootstrap. The prediction algorithms were then externally validated in an independent validation set consisting of participants of screening colonoscopy including 56 participants with CRC, 99 with AA and 99 controls without any colorectal neoplasms. Three different signatures for all-, early- and late-stage CRC consisting of five-, three- and eight-protein markers were obtained in the discovery set with areas under the curves (AUCs) after .632 + bootstrap adjustment of 0.85, 0.83 and 0.96, respectively. External validation in the representative screening population yielded AUCs of 0.79 (95% CI, 0.70–0.86), 0.79 (95% CI, 0.66–0.89) and 0.80 (95% CI, 0.70–0.89) for all-, early- and late-stage CRCs, respectively. The three-marker early-stage algorithm yielded an AUC of 0.65 (95% CI, 0.56–0.73) for detection of AA in the validation set. Although not yet competitive with available stool-based tests for CRC early detection, the identified proteins may contribute to the development of powerful blood-based tests for early detection of CRC and its precursors AAs. Graphical abstract: A three plasma protein biomarker signature derived in a clinical setting yielded an AUC of 0.83. When independently validated in a true screening setting (participants of screening colonoscopy) AUCs of 0.79 and 0.65 for distinguishing early stage colorectal cancer and advanced adenoma cases from controls free of neoplasms were obtained. These protein biomarkers may contribute to development of a blood based tests for population based screening. Image 1 Highlights: Participation rate is often low in endoscopy or stool-based colorectal cancer screening trials. Blood based test could be an alternative or supplement to existing screening procedures. With liquid chromatography-multiple reaction monitoring/mass spectrometry three stage specific signatures were identified. 3-marker signature detected early-stage colorectal cancer and advanced adenomas with area under the curves of 0.79 and 0.65. These proteins may serve as potential biomarkers for blood-based early detection of colorectal cancer and its precursors.