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

Abstract: PD53-08
Sources of Funding: None

Introduction

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._x000D_

Methods

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._x000D_

Results

We identified 5 candidate N-glycans significantly associated with GCT_x000D_ patients (A). The accuracy of the N-glycan score for GCT was significant with an area-under-the-curve (AUC) value of 0.87 (B). Diagnostically, the N-glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers (C). _x000D_ Prognostically, the N-glycan score was comprised 4 candidate N-glycans (D). The predictive value of the prognostic N-glycan score was significant, with an AUC value of 0.89 (E). A high value prognostic N-glycan score was significantly associated with poor prognosis (F)._x000D_ 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.

Conclusions

Our newly developed N-glycan score seems to be a practical diagnostic and prognostic method for GCT.

Funding

None

Authors
Takuma Narita
Shingo Hatakeyama
Tohru Yoneyama
Shintaro Narita
Shinichi Yamashita
Koji Mitsuzuka
Toshihiko Sakurai
Sadafumi Kawamura
Tatsuo Tochigi
Ippei Takahashi
Shigeyuki Nakaji
Yuki Tobisawa
Hayato Yamamoto
Takuya Koie
Norihiko Tsuchiya
Tomonori Habuchi
Yoichi Arai
Chikara Ohyama
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