Increased Serum Levels of Complement C3a Anaphylatoxin Indicate the Presence of Colorectal Tumors

Jens K. Habermann, Uwe J. Roblick, Brian T. Luke, Darue A. Prieto, William J.J. Finlay, Vladimir N. Podust, John M. Roman, Elisabeth Oevermann, Thomas Schiedeck, Nils Homann, Michael Duchrow, Thomas P. Conrads, Timothy D. Veenstra, Stanley K. Burt, Hans Peter Bruch, Gert Auer, Thomas Ried*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Background & Aims: Late diagnosis of colorectal carcinoma results in a significant reduction of average survival times. Yet despite screening programs, about 70% of tumors are detected at advanced stages (International Union Against Cancer stages III/IV). We explored whether detection of malignant disease would be possible through identification of tumor-specific protein biomarkers in serum samples. Methods: A discovery set of sera from patients with colorectal malignancy (n = 58) and healthy control individuals (n = 32) were screened for potential differences using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Candidate proteins were identified and their expression levels were validated in independent sample sets using a specific immunoassay (enzyme-linked immunosorbent assay). Results: By using class comparison and custom-developed algorithms we identified several m/z values that were expressed differentially between the malignant samples and the healthy controls of the discovery set. Characterization of the most prominent m/z values revealed a member of the complement system, the stable form of C3a anaphylatoxin (ie, C3a-desArg). Based on a specific enzyme-linked immunosorbent assay, serum levels of complement C3a-desArg predicted the presence of colorectal malignancy in a blinded validation set (n = 59) with a sensitivity of 96.8% and a specificity of 96.2%. Increased serum levels were also detected in 86.1% of independently collected sera from patients with colorectal adenomas (n = 36), whereas only 5.6% were classified as normal. Conclusions: Complement C3a-desArg is present at significantly higher levels in serum from patients with colorectal adenomas (P < .0001) and carcinomas (P < .0001) than in healthy individuals. This suggests that quantification of C3a-desArg levels could ameliorate existing screening tests for colorectal cancer.

Original languageEnglish
Pages (from-to)1020-1029
Number of pages10
JournalGastroenterology
Volume131
Issue number4
DOIs
StatePublished - Oct 2006
Externally publishedYes

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