Glycosylation status of serum immunoglobulin G in patients with prostate diseases.
Glycosylation status of serum immunoglobulin G in patients with prostate diseases.
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DOI：
10.1002/cam4.662
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发表时间：
2016-06
期刊：
影响因子：
4
通讯作者：
Fujimura T
中科院分区：
文献类型：
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作者：
Kazuno S;Furukawa J;Shinohara Y;Murayama K;Fujime M;Ueno T;Fujimura T
良性前列腺疾病患者的高值和高度可疑的癌症患者的低值的出现，降低了前列腺癌特异性抗原作为前列腺癌早期诊断标志物的可信度。在寻找其他互补标志物的过程中，我们重点研究了前列腺癌患者和正常人的血清免疫球蛋白。从正常人和前列腺病患者血清中提纯的免疫球蛋白用多肽N-葡聚糖酶消化。利用MALDI-飞行时间质谱仪对释放的多糖进行定量。我们报道前列腺癌患者免疫球蛋白重链中N-连接的(N‐acetylhexosamine)2(deoxyhexose)(mannose)3(N‐acetylglucosamine)2显著高于良性前列腺疾病患者和健康人，而(hexose)(N‐acetylhexosamine)2(deoxyhexose)(mannose)3(N-乙酰氨基葡萄糖)2在健康人和良性前列腺疾病患者的重链中更为丰富。因此，N-连接糖链末端己糖的缺失与前列腺癌的进展密切相关。此外，表面等离子体共振分析表明，前列腺癌患者的免疫球蛋白与接骨木凝集素的结合比良性前列腺疾病患者或正常人的结合减少，这表明患者免疫球蛋白的N-连接糖链中有较低水平的(N-乙酰神经氨酸)(α2-6)半乳糖/N-乙酰半乳糖胺基团。癌组麦胚凝集素与免疫球蛋白的结合率显著高于良性前列腺疾病组，但低于正常人。我们的研究表明，免疫球蛋白G的糖基化变化可以作为前列腺癌的有用诊断指标。
Occurrences of high values in patients with benign prostate disease and low values in patients with highly suspicious cancer have diminished the trustworthiness of prostate‐specific antigen as an early diagnostic marker of prostate cancer. In the search for other complimentary markers, we focused on serum IgG from patients with prostate diseases as well as normal subjects. IgG purified from the sera of normal control subjects and patients with prostate diseases, was digested with peptide N‐glycanase. Released glycans were quantified using MALDI‐time of flight mass spectrometry. We report that N‐linked (N‐acetylhexosamine)2(deoxyhexose)(mannose)3(N‐acetylglucosamine)2 was significantly increased in the IgG heavy chains of patients with prostate cancer compared with that of either benign prostatic disease patients or healthy subjects, whereas (hexose)(N‐acetylhexosamine)2(deoxyhexose)(mannose)3 (N‐acetylglucosamine)2 was more abundant in the heavy chains of healthy subjects and benign prostatic disease patients. Thus, an absence of the terminal hexose of N‐linked glycans has been closely connected to the progression of prostate cancer. Furthermore, surface plasmon resonance analyses have revealed that IgG from patients with prostate cancer has a decreased binding for Sambucus nigra lectin, compared with that from the benign prostatic disease patients or from normal subjects, suggesting lower levels of (N‐acetylneuraminic acid)(α2‐6)galactose/N‐acetylgalactosamine groups in the N‐linked glycans of patient IgG. Meanwhile, wheat germ agglutinin binding to IgG of the cancer group was significantly larger than that for the benign prostatic disease group but smaller than that for normal subjects. Our study indicates that the glycosylation changes in IgG can become useful diagnostic parameters for prostate cancer.