Open Access Highly Accessed Research article

A novel multiplex-protein array for serum diagnostics of colon cancer: a case–control study

Stefanie Bünger1, Ulrike Haug2, Maria Kelly4, Nicole Posorski5, Katja Klempt-Giessing1, Andrew Cartwright4, Stephen P Fitzgerald4, Vicki Toner4, Damien McAleer4, Timo Gemoll1, Tilman Laubert1, Jürgen Büning6, Klaus Fellermann6, Hans-Peter Bruch1, Uwe J Roblick1, Hermann Brenner3, Ferdinand von Eggeling5 and Jens K Habermann1*

Author affiliations

1 Laboratory for Surgical Research, Department of Surgery, University of Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany

2 Division of Preventive Oncology, National Center for Tumor Diseases/German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

3 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Bergheimer Str. 20, 69115, Heidelberg, Germany

4 Randox Laboratories GmbH, Wilhelmstr, 147a, 42489, Wulfrath, Germany

5 Core Unit Chip Application, Institute of Human Genetics, Jena University Hospital, Leutragraben 3, 07743, Jena, Germany

6 Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23528, Lübeck, Germany

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Citation and License

BMC Cancer 2012, 12:393  doi:10.1186/1471-2407-12-393

Published: 7 September 2012

Abstract

Background

More than 1.2 million new cases of colorectal cancer are reported each year worldwide. Despite actual screening programs, about 50% of the patients are diagnosed at advanced tumor stages presenting poor prognosis. Innovative screening tools could aid the detection at early stages and allow curative treatment interventions.

Methods

A nine target multiplex serum protein biochip was generated and evaluated using a training- and validation-set of 317 highly standardized, liquid nitrogen preserved serum samples comprising controls, adenomas, and colon cancers.

Results

Serum levels of CEA, IL-8, VEGF, S100A11, MCSF, C3adesArg, CD26, and CRP showed significant differences between cases and controls. The largest areas under the receiver operating characteristics curve were observed for CEA, IL-8, and CRP. At threshold levels yielding 90% specificity, sensitivities for CEA, IL-8 and CRP were 26%, 22%, and 17%, respectively. The most promising marker combinations were CEA + IL-8 reaching 37% sensitivity at 83% specificity and CEA + CRP with 35% sensitivity at 81% specificity. In an independent validation set CEA + IL-8 reached 47% sensitivity at 86% specificity while CEA + CRP obtained 39% sensitivity at 86% specificity. Early carcinomas were detected with 33% sensitivity for CEA + IL-8 and 28% for CEA + CRP.

Conclusions

Apart from CEA, IL-8, and CRP, the screening value of additional blood markers and the potential advantage of combining serum biochip testing with fecal occult blood testing needs to be studied. Multiplex biochip array technology utilizing serum samples offers an innovative approach to colorectal cancer screening.

Keywords:
Multiplex protein array biochip; Colon cancer screening; Serum diagnostics; High-throughput seromics; IL-8; CEA; CRP