Supporting Information: Table S1. Abbreviations and full names of the 92 protein biomarkers studied. Table S2. Head-to-head comparison of the diagnostic performance for 92 protein biomarkers Table S3. Eight-marker algorithm derived through the Lasso Logistic regression model. Table S4. Characteristics of study population in the independent validation set. Table S5. Comparison of significant biomarkers between current study and the study by Thorsen. Figure S1. The percentage of limit of detection (LOD) and missing data for each of 92 protein biomarkers in all the tested plasma samples. Figure S2. Box plots of plasma levels for 17 protein biomarkers: (a) between CRC cases and controls; (b) early stages (I/II) and advanced stage (III/IV) CRC. The bottom and top of the box indicate the first (Q1) and third (Q3) quartiles, and the middle line in the box is the median; the upper-limit equals Q3 plus 1.5 times interquartile range (IQR), and the lower-limit equals Q1 minus 1.5 times IQR.
ARTICLE ABSTRACT
Purpose: Novel noninvasive blood-based screening tests are strongly desirable for early detection of colorectal cancer. We aimed to conduct a head-to-head comparison of the diagnostic performance of 92 plasma-based tumor-associated protein biomarkers for early detection of colorectal cancer in a true screening setting.Experimental Design: Among all available 35 carriers of colorectal cancer and a representative sample of 54 men and women free of colorectal neoplasms recruited in a cohort of screening colonoscopy participants in 2005–2012 (N = 5,516), the plasma levels of 92 protein biomarkers were measured. ROC analyses were conducted to evaluate the diagnostic performance. A multimarker algorithm was developed through the Lasso logistic regression model and validated in an independent validation set. The .632+ bootstrap method was used to adjust for the potential overestimation of diagnostic performance.Results: Seventeen protein markers were identified to show statistically significant differences in plasma levels between colorectal cancer cases and controls. The adjusted area under the ROC curves (AUC) of these 17 individual markers ranged from 0.55 to 0.70. An eight-marker classifier was constructed that increased the adjusted AUC to 0.77 [95% confidence interval (CI), 0.59–0.91]. When validating this algorithm in an independent validation set, the AUC was 0.76 (95% CI, 0.65–0.85), and sensitivities at cutoff levels yielding 80% and 90% specificities were 65% (95% CI, 41–80%) and 44% (95% CI, 24–72%), respectively.Conclusions: The identified profile of protein biomarkers could contribute to the development of a powerful multimarker blood-based test for early detection of colorectal cancer. Clin Cancer Res; 21(14); 3318–26. ©2015 AACR.
