Clinical implications of serum N-glycan profiling as a diagnostic and prognostic biomarker in germ-cell tumors.
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.
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Takuma
T
Narita
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Shingo
http://orcid.org/0000-0002-0026-4079
S
Hatakeyama
Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Tohru
T
Yoneyama
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Shintaro
S
Narita
Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Shinichi
S
Yamashita
Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Koji
K
Mitsuzuka
Department of Urology, Yamagata University Graduate School of Medicine, Yamagata, Japan.
Toshihiko
T
Sakurai
Department of Urology, Miyagi Cancer Center, Natori, Japan.
Sadafumi
S
Kawamura
Department of Urology, Miyagi Cancer Center, Natori, Japan.
Tatsuo
T
Tochigi
Department of Social Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
Ippei
I
Takahashi
Department of Social Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
Shigeyuki
S
Nakaji
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Yuki
Y
Tobisawa
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Hayato
H
Yamamoto
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Takuya
T
Koie
Department of Urology, Yamagata University Graduate School of Medicine, Yamagata, Japan.
Norihiko
N
Tsuchiya
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Tomonori
T
Habuchi
Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Yoichi
Y
Arai
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.|Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Chikara
C
Ohyama
D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood / Q000175:diagnosis*; D011134:Polysaccharides / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D055815:Young Adult
D014408:Biomarkers, Tumor; D011134:Polysaccharides
Biomarker; germ-cell tumors; glycoblotting; mass spectrometry; serum N-glycan