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Significance of Serum N-glycan Profiling as a Diagnostic Biomarker in Urothelial Carcinoma

2016; Elsevier BV; Volume: 4; Issue: 3 Linguagem: Inglês

10.1016/j.euf.2016.11.004

2405-4569

M. Oikawa, Shingo Hatakeyama, Tohru Yoneyma, Yuki Tobisawa, Takuma Narita, Hayato Yamamoto, Yasuhiro Hashimoto, Takuya Koie, Shintaro Narita, Atsushi Sasaki, Norihiko Tsuchiya, Tomonori Habuchi, Ippei Takahashi, Shigeyuki Nakaji, Chikara Οhyama,

Glycosylation and Glycoproteins Research

The clinical diagnosis of urothelial carcinoma (UC) relies on invasive methods in patients with hematuria. Although more sensitive and noninvasive screening methods are required, a specific serum biomarker for UC is lacking.To examine whether serum glycan-based biomarkers can be applied to UC detection.Between April 1994 and June 2016, serum N-glycan concentrations were retrospectively measured in 212 patients with UC before treatment (UC group) and 212 pair-matched controls using glycoblotting and mass spectrometry.N-glycan levels were compared between the groups using receiver operating characteristic curves to select candidate N-glycans. We created an N-glycan score based on the combination of candidate N-glycans. The specificity and sensitivity of the candidate N-glycan score were evaluated using receiver operating characteristic curves.The N-glycan score was calculated using six N-glycans (m/z 1566, m/z 1687, m/z 1769, m/z 1871, m/z 2011, and m/z 2337) that were significantly associated with UC. The median N-glycan score was significantly higher in the UC group than in the pair-matched control group (5.0 vs 1.0, p<0.001). The N-glycan score correctly classified UC patients with a sensitivity, specificity, and area under the curve of 93%, 81%, and 0.95, respectively. The limitations of our study included its retrospective nature and nonclinical setting.Serum N-glycan content has the potential to be a specific and sensitive novel serum biomarker that may improve the accuracy of the detection for UC and reduce unnecessary invasive screening. Validation of this test in a large-scale prospective study is needed.Combination of serum N-glycan (N-glycan score) is a novel serum marker for urothelial carcinoma that is expressed by 93% of patients and thus is far more sensitive than classic urine cytology. Validation in a large patient cohort is needed.