Changes in cell surface protein glycosylation are common alterations that occur with tumor progression and reflect the use of many cancer biomarkers like PSA and CA19-9. However, identification of specific glycans associated with tumor regions is still poorly defined. Our group has developed a two-dimensional glycan tissue imaging mass spectrometry approach that can be used with any clinical formalin-fixed, paraffin-embedded tumor tissue used in pathology. Based on the analysis of over one thousand prostate cancer FFPE tissue blocks and tissue microarray samples across the spectrum of disease, it was found that the presence of multi-fucosylated branched N-glycans is associated with advanced tumors with neuroendocrine and metastatic features. These glycans are not present in indolent and lower-grade adenocarcinomas. The hypothesis currently being tested is to determine whether detection of higher numbers of these fucosylated structures predicts a worse prognosis for progressive metastatic disease. Race could be a factor for increased presentation at the time of diagnosis with more advanced disease. The goal of the present study was to assess whether more advanced tumors containing multi-fucosylated N-glycans are detected more frequently in a racial cohort of 307 samples. A series of 14 prostate tumor tissue microarrays (TMA) representing African-American (n=105), Hispanic (n=101) and Caucasian (n=101) subjects was evaluated with this method. The 307 individual tumor samples represented the spectrum of tumor stage, Gleason grade, and status of disease recurrence. For select cases, the original source tumor block tissues were analyzed to confirm the TMA core results. Each TMA slide was processed for antigen retrieval and peptide N-glycosidase F digestions to release N-glycans. Samples were analyzed by MALDI-FTICR mass spectrometry, and data were visualized and analyzed by SCiLS Lab software. Tumor tissues having increased levels of fucosylation were detected in each cohort, but with an overall increase in numbers detected in the African-American cohort. Multitiered analyses are ongoing to identify glycan signatures associated with age, grade, stage, race, and recurrence. In summary, the presence and detection of a distinct panel of multi-fucosylated tissue N-glycans associated with the most lethal forms of prostate cancer can be detected in low-grade tumor samples at the time of diagnosis. This could be developed into a tissue-based prognostic biomarker panel to be applied at the time of initial diagnosis, and impact earlier treatment decisions.
Citation Format: Richard R. Drake, Fred David, Cameron Miller, Melanie Jefferson, Laura Spruill, Michael Liss, Brandi Weaver, Peggi M. Angel, Robin Leach, Chanita Hughes-Halbert. Distinguishing lethal from indolent prostate cancer using N-glycan imaging mass spectrometry in a racial tissue microarray cohort [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C032.