Significance of serum N-glycan profiling as a diagnostic marker in testicular germ cell tumor.

Abstract

489 Background: Specific tumor marker for seminoma is still lacking. Moreover, 10% to 15% of the patients with non-seminomatous germ cell tumor (NSGCT) can be expected to have normal marker levels. Glycan-based biomarkers for testicular germ cell tumor (TGCT) have not yet been established. We examined whether the serum N-glycan profiling can be applied to detection in patient with TGCT. Methods: We performed a N-glycan structural analysis of sera from 14 patients with GCT and age-matched 28 healthy volunteers using the glycoblotting methods and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The intensity of the N-glycans was compared between the TGCT patients and the volunteers to select TGCT associate N-glycans. Optimal cut-off values were determined by receiver operating characteristic (ROC) curves. Selected N-glycans were divided according to cut-off values, and positive numbers of TGCT associated N-glycan was added up to risk classification. Results: Six (43%) had seminoma, and eight (57%) patients had NSGCT in this study. The numbers of patients in stage I, II, III were 5, 2, and 4, respectively. Three patients had extragonadal tumor. The numbers of patients in IGCCC good, intermediate and poor risk were 10, 1, and 3, respectively. There were 3 patients (21%) with negative in any tumor markers. We identified 70 kinds of N-glycans in sera from healthy volunteers and GCT patients. A total 6 of N-glycans; m/z 2336.85, 2378.86, 2890.05, 3195.16, 3341.22, 3560.30 were selected as significantly high intensity in the patient with TGCT than in the healthy volunteers, with the area under the curve (AUC) of 0.81, 0.83, 0.86, 0.84, 0.81, and 0.78, respectively. Tumor associated N-glycans were classified as positive or negative, and scored from 0 to 6 points. Optimal cut-off score for detection was determined by ROC curve, and score > 3 were selected (AUC 0.90, P < 0.001). Based on this classification, 2 of 3 patients with negative tumor markers were categorized as a carrier for TCGT. Conclusions: Although the present study is small and preliminary, serum N-glycan analysis is a potential approaches to discover new biomarkers for TGCT. Further validation study is warranted.