In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 415-415
Abstract:
415 Background: Colorectal cancer (CRC) is the third most frequent cancer disease in the US. As the 5 year survival is closely associated to stage of disease at the time of diagnosis, patients with localized tumor limited to the colon or rectum have more than 90% chance of 5 year survival, while tumors spreading to regional lymph nodes or to distant organs, have a 5 year survival rate of 69% and 12%, respectively. Since late diagnosis is equal to a poor prognosis for the patients, biomarker guided early detection could make a difference for these patients. One strategy is blood based assays, where we hypothesis that a tumor and its microenvironment will lead to a deposition of specific proteins in the blood. However, due to the complexity of plasma, it is not only a biological but also a technical challenge to detect the proteins specific for CRC. Consequently, we combined the technical evaluation of multiplex proximity probing assays (PPA) with the search for relevant biomarkers for CRC. Each of the protein assays were based on thorough literature studies on the biology of CRC. Methods: Proteins were measured using multiplex PPA. Each assay was constructed from commercially available antibodies conjugated to two DNA oligonucleotides. When the antibodies from one assay bind the target protein simultaneously, it enables the DNA oligonucleotides to be either enzymatic ligated or extended to a PCR amplicon. This PCR amplicon reflects the identity of the proteins and can be quantified by real-time PCR. We evaluated the assays and searched for potential early markers using a collection of case-control plasma samples from a larger endoscopy study. In total we measure the levels of 150 different proteins in 296 human plasma samples from 74 CRC patients, 74 healthy individuals, 74 adenoma patients, and 74 patients with non-cancer diseases. Results: We have a successrate of 80%, the sensitivity is for most assays below 5 pM, and we find no cross-reactivity in chicken plasma for any of the assays. We previous reported that CEA, TIMP-1, CA242, and IL8 were upregulated in CRC plasma. These proteins were also identified in our extended study and the data will be presented. Conclusions: We find potential early markers, which we will validate in new sample material.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.4_suppl.415
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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