Strategies to improve the early diagnosis of prostate cancer will provide opportunities for earlier intervention. The blood-based prostate-specific antigen (PSA) assay is widely used for prostate cancer diagnosis but specificity of the assay is not satisfactory. An algorithm based on serum levels of PSA combined with other serum biomarkers may significantly improve prostate cancer diagnosis. Plasma glycan-binding IgG/IgM studies suggested that glycan patterns differ between normal and tumor cells. We hypothesize that in prostate cancer glycoproteins or glycolipids are secreted from tumor tissues into the blood and induce auto-immunoglobulin (Ig) production. A 24-glycan microarray and a 5-glycan subarray were developed using plasma samples obtained from 35 prostate cancer patients and 54 healthy subjects to identify glycan-binding auto-IgGs. Neu5Acα2-8Neu5Acα2-8Neu5Acα (G81)-binding auto-IgG was higher in prostate cancer samples and, when levels of G81-binding auto-IgG and growth differentiation factor-15 (GDF-15 or NAG-1) were combined with levels of PSA, the prediction rate of prostate cancer increased from 78.2% to 86.2% than with PSA levels alone. The G81 glycan-binding auto-IgG fraction was isolated from plasma samples using G81 glycan-affinity chromatography and identified by N-terminal sequencing of the 50 kDa heavy chain variable region of the IgG. G81 glycan-binding 25 kDa fibroblast growth factor-1 (FGF1) fragment was also identified by N-terminal sequencing. Our results demonstrated that a multiplex diagnostic combining G81 glycan-binding auto-IgG, GDF-15/NAG-1 and PSA (≥ 2.1 ng PSA/ml for cancer) increased the specificity of prostate cancer diagnosis by 8%. The multiplex assessment could improve the early diagnosis of prostate cancer thereby allowing the prompt delivery of prostate cancer treatment.

中文翻译：

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血浆聚糖结合自身 IgG 生物标志物的水平提高了前列腺癌诊断的准确性。

改善前列腺癌早期诊断的策略将为早期干预提供机会。基于血液的前列腺特异性抗原 (PSA) 检测广泛用于前列腺癌诊断，但检测的特异性并不令人满意。基于 PSA 血清水平结合其他血清生物标志物的算法可能会显着改善前列腺癌的诊断。血浆聚糖结合 IgG/IgM 研究表明，正常细胞和肿瘤细胞之间的聚糖模式不同。我们假设在前列腺癌中糖蛋白或糖脂从肿瘤组织分泌到血液中并诱导自身免疫球蛋白 (Ig) 的产生。使用从 35 名前列腺癌患者和 54 名健康受试者获得的血浆样本开发了 24 聚糖微阵列和 5 聚糖亚阵列，以识别聚糖结合自身 IgG。Neu5Acα2-8Neu5Acα2-8Neu5Acα (G81) 结合自身 IgG 在前列腺癌样本中更高，并且当 G81 结合自身 IgG 和生长分化因子-15（GDF-15 或 NAG-1）水平与PSA，前列腺癌的预测率比单独的 PSA 水平从 78.2% 提高到 86.2%。使用 G81 聚糖亲和层析从血浆样品中分离 G81 聚糖结合自身 IgG 级分，并通过 IgG 的 50 kDa 重链可变区的 N 端测序进行鉴定。G81 聚糖结合 25 kDa 成纤维细胞生长因子-1 (FGF1) 片段也通过 N 端测序鉴定。我们的结果表明，结合 G81 聚糖结合自身 IgG、GDF-15/NAG-1 和 PSA（≥ 2.1 ng PSA/ml 用于癌症）的多重诊断将前列腺癌诊断的特异性提高了 8%。