Immunogenic sugar moieties of prostate cancers

描述（由申请人提供）：该项目汇集了在碳水化合物微阵列高通量平台、新糖脂（NGL）技术与质谱分析相结合的碳水化合物配体发现、用于高灵敏度检测细胞和血清标记物的流式细胞术（Hi-D FACS）以及检测前列腺特异性抗原（PSA）的第一个国际标准方面建立了研究记录的研究人员。该团队的主旨是免疫生物标志物的识别和表征，以及开发用于临床和研究应用的高灵敏度检测方法。该项目的最终目标是确定用于检测前列腺癌和监测癌症进展的新型血清生物标志物。在初步研究中，他们在前列腺癌中发现了许多基于碳水化合物的生物标志物。此外，他们还使用碳水化合物微阵列检测到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具有免疫原性，并且能够在前列腺癌受试者中诱导特异性自身抗体。检测血清中的此类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前列腺癌组织库中保存的大量分类良好的血清和组织标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非正常表达的 A/-聚糖的特异性抗碳水化合物自身抗体是否可以区分 BPH 男性和前列腺癌和/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特异性血清抗体，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) 确定被mAb 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-聚糖序列； 5) 使用新型血清学标志物建立高度灵敏且用户友好的免疫测定法，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.