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

摘要

Abstract 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.