TY  - JOUR
AU  - Bhardwaj, Megha
AU  - Gies, Anton
AU  - Weigl, Korbinian
AU  - Tikk, Kaja
AU  - Benner, Axel
AU  - Schrotz-King, Petra
AU  - Borchers, Christoph H
AU  - Brenner, Hermann
TI  - Evaluation and Validation of Plasma Proteins Using Two Different Protein Detection Methods for Early Detection of Colorectal Cancer.
JO  - Cancers
VL  - 11
IS  - 10
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2019-02319
SP  - 1426
PY  - 2019
AB  - Plasma protein biomarkers could be an efficient alternative for population-based screening for early detection of colorectal cancer (CRC). The objective of this study was to evaluate and validate plasma proteins individually and as a signature for early detection of CRC.In a three-stage design, proteins were measured firstly by liquid chromatography/multiple reaction monitoring-mass spectrometry (LC/MRM-MS) and later by proximity extension assay (PEA) in a discovery set consisting of 96 newly diagnosed CRC cases and 94 controls free of neoplasms at screening colonoscopy. Two algorithms (one for each measurement method) were derived by Lasso regression and .632+ bootstrap based on 11 proteins that were included in both the LC/MRM-MS and PEA measurements. Additionally, another algorithm was constructed from the same eleven biomarkers plus amphireglin, the most promising protein marker in the PEA measurements that had not been available from the LC/MRM-MS measurements. Lastly the three prediction signatures were validated with PEA in independent samples of participants of screening colonoscopy (CRC (n = 56), advanced adenoma (n = 101), and participants free of neoplasm (n = 102)).The same four proteins were included in all three prediction signatures; mannan binding lectin serine protease 1, osteopontin, serum paraoxonase lactonase 3 and transferrin receptor protein 1, and the third prediction signature additionally included amphiregulin. In the independent validation set from a true screening setting, the five-marker blood-based signature including AREG presented areas under the curves of 0.82 (95
LB  - PUB:(DE-HGF)16
C6  - pmid:31557860
DO  - DOI:10.3390/cancers11101426
UR  - https://inrepo02.dkfz.de/record/147183
ER  -