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
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
收藏
页码:739 / 748
页数:10
相关论文
共 22 条
[21]   Diagnosis and activity assessment of immunoglobulin A nephropathy: current perspectives on noninvasive testing with aberrantly glycosylated immunoglobulin A-related biomarkers [J].
Suzuki, Yusuke ;
Suzuki, Hitoshi ;
Makita, Yuko ;
Takahata, Akiko ;
Takahashi, Keiko ;
Muto, Masahiro ;
Sasaki, Yohei ;
Kelimu, Atikemu ;
Matsuzaki, Keiichi ;
Yanagawa, Hiroyuki ;
Okazaki, Keiko ;
Tomino, Yasuhiko .
INTERNATIONAL JOURNAL OF NEPHROLOGY AND RENOVASCULAR DISEASE, 2014, 7 :409-414
[22]  
vansDijk W., 1995, GLYCOCONJ J, V12, P227