C-reactive protein as a parameter for defining normal blood samples in identification and evaluation of serological biomarkers

초록

Selecting normal control samples is critical for the identification and evaluation of serum biomarker proteins; however, currently few inclusion parameters have been identified. In this paper, we investigated whether serum C-reactive protein (CRP) levels are a suitable inclusion parameter to define normal controls. We analyzed serum alpha-fetoprotein (AFP), cytokeratin 19 fragment (CYFRA 21-1), intercellular adhesion molecule 1 (ICAM-1), and fibronectin expression levels from normal individuals (n=97) and patients with hepatocellular carcinoma (n=36), lung cancer (n=50), and colorectal cancer (n=30). Receiver operating characteristic (ROC) analysis of the biomarker proteins was performed using four different control groups (C1-C4) with increasing serum CRP levels. The biomarker expression levels were higher in all three sets of cancer patients when compared with control groups C1 through C3. The AUC, sensitivity, and specificity values of the biomarkers dramatically decreased with increasing CRP levels in the control groups. These results suggest that the serum CRP level affects downstream ROC analysis, and that CRP levels could be used as a control inclusion parameter to define normal samples for identifying and evaluating serum cancer biomarkers.

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