Immunogenic sugar moieties of prostate cancers

描述(由申请人提供)：该项目汇集了在高通量平台上建立研究记录的研究人员，这些平台包括碳水化合物微阵列、新糖脂(NGL)技术和用于发现碳水化合物配体的质谱仪、用于高灵敏度检测细胞和血清标志物的流式细胞仪(Hi-D FACS)，以及第一个用于检测前列腺特异性抗原(PSA)的国际标准。该团队的主要任务是识别和表征免疫生物标记物，并为临床和研究应用开发高灵敏度的分析方法。该项目的最终目标是确定新的血清生物标志物，用于前列腺癌的检测和癌症进展的监测。在初步调查中，他们已经在前列腺癌中确定了一些基于碳水化合物的生物标记物。此外，他们还使用碳水化合物微阵列检测到了其中一些的自身抗体。他们假设，这些异常表达的碳水化合物是免疫原性的，能够在前列腺癌受试者中诱导特定的自身抗体。检测血清中的这种抗体可以检测前列腺癌及其侵袭性进展。在这个项目中，合作小组计划通过表征保存在前列腺癌组织库中的大量分类良好的血清和组织样本来检验他们的假设。他们计划1)确定针对甘露糖簇和其他不正常表达的A/-糖链的抗碳水化合物自身抗体是否可以区分患有BPH和前列腺癌的男性和/或预测侵袭性和进展性前列腺癌；2)确定前列腺癌受试者中是否存在针对其他碳水化合物自身抗原的血清抗体，并评估其诊断和预后价值；3)确定个体血清中某些抗碳水化合物抗体的存在是否与前列腺癌中相应糖表位的异常表达相关；4)确定单抗AE3和G1识别的HCA和其他癌症相关糖蛋白的糖表位的碳水化合物O-糖链序列；以及5)使用新的血清学标记建立高灵敏度和用户友好的免疫分析方法，以促进前列腺癌的大规模临床研究。

DESCRIPTION (provided by applicant): This project brings together researchers who have established research track records in high-throughput platforms of carbohydrate microarrays, neoglycolipid (NGL) technology coupled with mass spectrometry for carbohydrate ligand discovery, flow cytometry (Hi-D FACS) for highly-sensitive detection of cell and serum markers, and the first international standard for detection of prostate-specific antigen (PSA). The thrust of this team is identification and characterization of immunological biomarkers and development of highly sensitive assays for clinical and research applications. The ultimate goal of this project is to identify novel serum biomarkers for detection of prostate cancer and monitoring of cancer progression. In preliminary investigations, they have identified a number of carbohydrate-based biomarkers in prostate cancers. In addition, they have detected autoantibodies to some of these using carbohydrate microarrays. They hypothesize that these aberrantly expressed carbohydrates are immunogenic and are able to induce specific autoantibodies in prostate cancer subjects. Detection of such antibodies in serum could allow detection of prostate cancer and its aggressive progression. In this project, collaborating group plan to examine their hypotheses by characterizing a large-collection of well-categorized serum and tissue specimens preserved in their prostate cancer tissue banks. They plan to 1) determine whether anti-carbohydrate autoantibodies specific for Mannose-clusters and other A/-glycans not normally expressed can distinguish between men with BPH and prostate cancer and/or predict the aggressive and progressive prostate cancers; 2) determine whether serum antibodies specific for other carbohydrate autoantigens are present in prostate cancer subjects and evaluate their diagnostic and prognostic values; 3) determine whether the presence of certain anti-carbohydrate antibodies in the serum of an individual correlates with the aberrant expression of corresponding glyco-epitopes in the prostate cancer; 4) determine the carbohydrate O-glycan sequences of glyco-epitopes of HCA and other cancer-associated glycoproteins that are recognized by mAb AE3 and G1; and 5) establish highly sensitive and user-friendly immunoassays using novel serological markers to facilitate a large-scale clinical study of prostate cancer.