Clinical implications of serum N-glycan profiling as a diagnostic and prognostic biomarker in germ-cell tumors

被引：23

作者：

Narita, Takuma ^{[1
]}

Hatakeyama, Shingo ^{[1
]}

Yoneyama, Tohru ^{[2
]}

Narita, Shintaro ^{[3
]}

Yamashita, Shinichi ^{[4
]}

Mitsuzuka, Koji ^{[4
]}

Sakurai, Toshihiko ^{[5
]}

Kawamura, Sadafumi ^{[6
]}

Tochigi, Tatsuo ^{[6
]}

Takahashi, Ippei ^{[7
]}

Nakaji, Shigeyuki ^{[7
]}

Tobisawa, Yuki ^{[1
]}

Yamamoto, Hayato ^{[1
]}

Koie, Takuya ^{[1
]}

Tsuchiya, Norihiko ^{[5
]}

Habuchi, Tomonori ^{[3
]}

Arai, Yoichi ^{[4
]}

Ohyama, Chikara ^{[1
,2
]}

机构：

[1] Hirosaki Univ, Grad Sch Med, Dept Urol, 5 Zaifu Chou, Hirosaki, Aomori 0368562, Japan

[2] Hirosaki Univ, Grad Sch Med, Dept Adv Transplant & Regenerat Med, Hirosaki, Aomori, Japan

[3] Akita Univ, Grad Sch Med, Dept Urol, Akita, Japan

[4] Tohoku Univ, Grad Sch Med, Dept Urol, Sendai, Miyagi, Japan

[5] Yamagata Univ, Grad Sch Med, Dept Urol, Yamagata, Japan

[6] Miyagi Canc Ctr, Dept Urol, Natori, Miyagi, Japan

[7] Hirosaki Univ, Sch Med, Dept Social Med, Hirosaki, Aomori, Japan

来源：

CANCER MEDICINE | 2017年 / 6卷 / 04期

基金：

日本学术振兴会;

关键词：

Biomarker; germ-cell tumors; glycoblotting; mass spectrometry; serum N-glycan; CANCER; GLYCOSYLATION;

D O I：

10.1002/cam4.1035

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：739 / 748

页数：10

共 22 条

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