The use of glycan serum biomarkers for the detection of cancer

A42 The Use of Glycan Serum Biomarkers for the Detection of CancerSuzanne Miyamoto 1 , Hyun Joo An 2 , Crystal Kirmiz 2 , Bensheng Li 2 , Caroline Chu 2 , Hao Liu 2 , Anthony Ferrige 4 , Robert Alecio 4 , Helen Chew 1 , Gary Leiserowitz 3 , Ralph deVere White 1 , Kit S Lam 1 and Carlito B Lebrilla 2 . 1 UC Davis Cancer Center, Sacramento, CA; 2 UC Davis, Davis, CA; 3 UC Davis Medical Center, Sacramento, CA; 4 Positive Probability Limited, Isleham, UK.During the development of cancer, tumor cells alter glycosylation of proteins leading to changes in the growth, adhesion, signaling, and immune surveillance of the tumor. These glycosylation changes are known to correlate with increasing tumor burden and poor prognosis. Current immunochemical tests for cancer biomarkers, which include CA125, CA 15-3 or CA 19-9 are antibody-based assays for glycosylated proteins often associated with ovarian, breast cancer or other cancer types. These tests are not specific or sensitive enough for early detection of cancer and are not recommended by the American Society of Clinical Oncology for this purpose. As an adjunct to current immunochemical, proteomic or other methods for detection and diagnosis of cancer in patient serum, we have developed methods to chemically cleave oligosaccharides (glycans) from their protein cores that are present in serum samples. The resulting free glycan species are then analyzed by matrix-assisted laser desorption ionization (MALDI) or electrospray ionization (ESI) Fourier Transform Mass Spectrometry (FTMS). Further structural analysis of the glycans can be performed in the FTMS through the use of tandem mass spectrometry with infrared multi-photon dissociation (IRMPD) to sequence and confirm their oligosaccharide identification and core structure. Based on this analysis, glycan profiles are being created that will represent the glycosylation changes associated with the cancer disease state of the patient, which are sufficiently different from cancer free or "normal" patient serum. These glycan profiles will contain distinct glycan biomarkers that we hope can be "signatures of cancer". We are using these methods to determine if we can detect significant glycan differences in the serum of ovarian, breast or prostate cancer patients that are not found in non-cancer patients. We have already analyzed condition media from tumor cell lines and cancer patient serum samples and have identified a panel of potential glycan cancer biomarkers that appear to correlate with the presence of cancer. We are in the process of determining whether these serum glycan biomarkers correlate with disease state. We envision that this test can be used as a diagnostic aid or to monitor treatment or predict outcome. This glycan profile test must be sensitive, specific and reproducible in order to take this technology from the laboratory bench to the bedside of the cancer patient.