Clinical implications of serum N-glycan profiling as a diagnostic and prognostic biomarker in germ-cell tumors.
Clinical implications of serum N-glycan profiling as a diagnostic and prognostic biomarker in germ-cell tumors.
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DOI：
10.1002/cam4.1035
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发表时间：
2017-04
期刊：
影响因子：
4
通讯作者：
Ohyama C
中科院分区：
文献类型：
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作者：
Narita T;Hatakeyama S;Yoneyama T;Narita S;Yamashita S;Mitsuzuka K;Sakurai T;Kawamura S;Tochigi T;Takahashi I;Nakaji S;Tobisawa Y;Yamamoto H;Koie T;Tsuchiya N;Habuchi T;Arai Y;Ohyama C
血清生物标志物监测对于生殖细胞肿瘤（GCT）的管理至关重要。然而，并不是所有的GCT都对常规肿瘤标志物呈阳性。我们研究了血清N-聚糖生物标志物是否可用于GCT患者的检测和预后。我们使用糖印迹法和质谱法对来自54名未经治疗的GCT患者和103名年龄调整的健康志愿者的血清进行了全面的N-聚糖结构分析。从具有最高相关性的N-聚糖中选择候选N-聚糖;确定临界浓度值，并基于存在的阳性N-聚糖数量创建N-聚糖评分。使用受试者工作特征（ROC）曲线分析该评分对诊断和预后的有效性。我们确定了五种与GCT患者显著相关的候选N-聚糖。GCT的N-聚糖评分的准确性非常显着，曲线下面积（AUC）值为0.87。在诊断方面，N-聚糖评分检测到12例常规肿瘤标志物阴性患者中的10例（83%）。在预后方面，N-聚糖评分包括4种候选N-聚糖。预后N-聚糖评分的预测值显著，AUC值为0.89。高值预后N-聚糖评分与预后不良显著相关。最后，为了鉴定潜在的载体蛋白，对血清的免疫球蛋白（IG）组分进行N-聚糖分析，并与全血清进行比较。IG-组分中的候选N-聚糖显著减少;因此，候选N-聚糖的载体蛋白可能不是免疫球蛋白。总之，我们新开发的N-聚糖评分似乎是GCT的实用诊断和预后方法。
Serum biomarker monitoring is essential for management of germ‐cell tumors (GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N‐glycan‐based biomarkers can be applied for detection and prognosis in patients with GCT. We performed a comprehensive N‐glycan structural analysis of sera from 54 untreated GCT patients and 103 age‐adjusted healthy volunteers using glycoblotting methods and mass spectrometry. Candidate N‐glycans were selected from those with the highest association; cutoff concentration values were established, and an N‐glycan score was created based on the number of positive N‐glycans present. The validity of this score for diagnosis and prognosis was analyzed using a receiver operating characteristic (ROC) curve. We identified five candidate N‐glycans significantly associated with GCT patients. The accuracy of the N‐glycan score for GCT was significant with an area‐under‐the‐curve (AUC) value of 0.87. Diagnostically, the N‐glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers. Prognostically, the N‐glycan score comprised four candidate N‐glycans. The predictive value of the prognostic N‐glycan score was significant, with an AUC value of 0.89. A high value prognostic N‐glycan score was significantly associated with poor prognosis. Finally, to identify a potential carrier protein, immunoglobulin (Ig) fractions of sera were subjected to N‐glycan analysis and compared to whole sera. Candidate N‐glycans in Ig‐fractions were significantly decreased; therefore, the carrier protein for candidate N‐glycans is likely not an immunoglobulin. In summary, our newly developed N‐glycan score seems to be a practical diagnostic and prognostic method for GCT.