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. 2017 Oct 31:9:517-526.
doi: 10.2147/CLEP.S144171. eCollection 2017.

Development and validation of a panel of five proteins as blood biomarkers for early detection of colorectal cancer

Hongda Chen  1   2 , Jing Qian  1 , Simone Werner  1 , Katarina Cuk  1 , Phillip Knebel  3 , Hermann Brenner  1   4   5
Affiliations

Development and validation of a panel of five proteins as blood biomarkers for early detection of colorectal cancer

Hongda Chen et al. Clin Epidemiol. .

Abstract

Objective: Reliable noninvasive biomarkers for early detection of colorectal cancer (CRC) are highly desirable for efficient population-based screening with high adherence rates. We aimed to discover and validate blood-based protein markers for the early detection of CRC.

Patients and methods: A two-stage design with a discovery and a validation set was used. In the discovery phase, plasma levels of 92 protein markers and serum levels of TP53 autoantibody were measured in 226 clinically recruited CRC patients and 118 controls who were free of colorectal neoplasms at screening colonoscopy. An algorithm predicting the presence of CRC was derived by Lasso regression and validated in a validation set consisting of all available 41 patients with CRC and a representative sample of 106 participants with advanced adenomas and 107 controls free of neoplasm from a large screening colonoscopy cohort (N=6018). Receiver operating characteristic (ROC) analyses were conducted to evaluate the diagnostic performance of individual biomarkers and biomarker combinations.

Results: An algorithm based on growth differentiation factor 15 (GDF-15), amphiregulin (AREG), Fas antigen ligand (FasL), Fms-related tyrosine kinase 3 ligand (Flt3L) and TP53 autoantibody was constructed. In the validation set, the areas under the curves of this five-marker algorithm were 0.82 (95% CI, 0.74-0.90) for detecting CRC and 0.60 (95% CI, 0.52-0.69) for detecting advanced adenomas. At cutoffs yielding 90% specificity, the sensitivities (95% CI) for detecting CRC and advanced adenomas were 56.4% (38.4%-71.8%) and 22.0% (13.4%-35.4%), respectively. The five-marker panel showed similar diagnostic efficacy for the detection of early- and late-stage CRC.

Conclusion: The identified most promising biomarkers could contribute to the development of powerful blood-based tests for CRC screening in the future.

Keywords: adenoma; amphiregulin; colorectal cancer; growth differentiation factor 15; screening.

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Conflict of interest statement

Disclosure Hermann Brenner and Hongda Chen have applied for a patent “Biomarker panel for diagnosing cancer.” The other authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
STARD diagram showing the selection of study participants enrolled in the BLITZ study during 2005–2015 and the analysis scheme. Abbreviations: CRC, colorectal cancer; STARD, STAandards for the Reporting of Diagnostic accuracy studies.
Figure 2
Figure 2
Comparison of ROC curves of the four- and five-marker panel for detecting: (A) CRC vs controls free of neoplasm; (B) advanced adenomas vs controls free of neoplasm. Abbreviations: AUC, area under the curve; CRC, colorectal cancer; ROC, receiver operating characteristic.
Figure 3
Figure 3
Comparison of ROC curves of (A) the four-marker panel and (B) five-marker panel for detecting early- and late-stage CRCs. Abbreviations: AUC, area under the curve; CRC, colorectal cancer; ROC, receiver operating characteristic.
See this image and copyright information in PMC

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