Method for early detection of pancreatic cancer: Study

Mostly because it is diagnosed much later in life, pancreatic cancer is one of the most deadly types of the disease. For screens aimed at early detection, current markers are too vague and insensitive. Now, a study team has published a new technique in the journal Angewandte Chemie that could result in a diagnosis that is far more accurate and reliable. This method relies on the targeted detection of specific antibodies in blood samples.

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Detecting pancreatic cancer

Pancreatic cancer is one of the most deadly forms of the disease, mainly because it is detected quite late in life. Current markers are overly sensitive and confusing for screening for early detection. Recently, a research team has released a unique technique in the journal Angewandte Chemie that could lead to a diagnosis that is much more reliable and accurate. This technique is based on the specific recognition of antibodies present in a blood sample.

They chose to use autoantibodies directed against the tumor-associated form of mucin-1 (TA-MUC1). Mucin-1 is a highly glycosylated protein (protein with sugar components) that is found, for example, in glandular tissue. In many types of tumors, including pancreatic cancer, it is found in significantly higher concentrations. In addition, the pattern of glycosylation is different from the normal form. The team’s goal was to find autoantibodies that are specifically directed against TA-MUC1 and are a clear indicator of pancreatic cancer.

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Based on structural analysis and computer simulations of known antibodies against TA-MUC1 (SM3 and 5E5), the team designed a collection of synthetic glycopeptides that mimic different segments (epitopes) of TA-MUC1. They also made unnatural modifications to increase the chances of identifying autoantibody subgroups indicative of the disease. The team immobilized these model antigens on gold nanoparticles and obtained probes suitable for a serological assay (dot-blot assay). The diagnostic assay was validated with real samples from patients with pancreatic cancer and a healthy control group. Some of the nanoparticle probes could distinguish very well between samples from diseased and healthy individuals

Probes with small glycopeptide antigens that correspond to only one epitope gave better results than larger probes mimicking multiple epitopes – an advantage for easier synthetic production. A small glycopeptide with an unnatural modification in its sugar component was found to be particularly effective for discriminatory autoantibody detection. This new structure-based approach may help in the selection of autoantibody subgroups with high tumor specificity.

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