BackgroundMore 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.MethodsA 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.ResultsSerum 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.ConclusionsApart 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.
The semiautomated Evidence Investigator has been applied to the simultaneous specific measurement of soluble adhesion molecules: L-, P-, E- selectins, VCAM-1, ICAM-1 using a reduced volume of sample. The biochip is the solid support and vessel where the sandwich immunoassay takes place. Signal detection, imaging, data processing, and storage are fully automated. Calibration curves are generated simultaneously for each analyte, with automatic validation against supplied calibration data. These curves are used for the calculation of the concentrations in multi-analyte controls and human serum samples. Data from the evaluation parameters assessed indicate suitability of the Evidence Investigator system for the application.
Simultaneous Detection of Colorectal Cancer Mutations in Stool Samples with Biochip ArraysColorectal cancer (CRC) is the second main cause of cancer-related death in the Western world and like many other tumours is curable if detected at an early stage. Current detection options include faecal occult blood testing and invasive direct visualisation techniques such as flexible sigmoidoscopy, colonoscopy and barium enema. The availability of a more simple, non-invasive test that detects tumour specific products with optimal analytical performance might overcome barriers among patients who are not willing to undergo more sensitive but invasive tests. One such emerging technology, which has shown promise in recent years, is the analysis of DNA alterations exfoliated from tumour cells into stool. Here we report an analytical platform for non-invasive detection of 28 common mutations within CRC-related genesAPC, TP53, K-rasandBRAFin stool samples based on biochip array technology and applied to the semi-automated Evidence Investigator analyser. Mutation detection was possible in 1000-fold excess of wildtype DNA and analysis of 10 CRC-positive patient samples showed presence of targeted mutations with equivalent mutations also identified by an alternative method. This application represents an excellent tool for the multiplex detection of CRC-specific mutations using a single platform.
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