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.