Abstract
Purpose: To develop novel diagnostic biomarkers for Bladder Cancer (BC), we concurrently evaluated serum and urine glycans in BC patients by utilizing a recently established glycoblotting method. Experiments: N- and O-glycan levels in whole serum from 45 and 13 male patients diagnosed with BC were analyzed. As a control, 29 and 10 patients with benign prostatic hyperplasia (BPH) were also studied and the results were compared. Furthermore, urine N- and O-glycome from 8 patients with muscle-invasive BC and 11 with BPH were analyzed. In serum N-glycome analysis the area-under-the-curve (AUC) value was calculated by in house R software. In the other cases JMP, version 10.0.2 software package (SAS, Cary, NC) was used and p <0.05 was considered statistically significant. Results: The expression level of three N-glycans significantly increased in sera of BC patients. All of them had highly branched and sialylated structures with core-Fuc. The levels of three O-glycans were significantly higher in BC than in the control. In examination of urine samples, 16 N-glycans were significantly elevated in BC as compared to the control. Although 11 O-glycans were detected in urine samples, there was no significant difference in the expression levels. Conclusions: The levels of highly branched, sialylated N-glycans and early sialylated O-glycans were increased in sera of BC patients. Moreover, we found that N-glycans increased in urine more than in serum of BC patients. These results suggest that the glycome change in urine directly results from glycoproteins that exist in BC cells. Thus, further large-scale glycan profiling will provide novel biomarkers for diagnosing BC in the near future.
Highlights
The human body consists of approximately 60 billion of cells, which are totally covered with carbohydrate chains
11 O-glycans were detected in urine samples, there was no significant difference in the expression levels
The levels of highly branched, sialylated N-glycans and early sialylated O-glycans were increased in sera of Bladder Cancer (BC) patients
Summary
The human body consists of approximately 60 billion of cells, which are totally covered with carbohydrate chains. It is estimated that over 70% of all human proteins are glycosylated [1].Glycans are known to have crucial roles in the molecular recognition and adhesion between cells and the disorder of this function affects greatly to the abnormality in human body. In order to resolve this problem, a new technology for glycan-specific enrichment, the “glycoblotting method”, was developed recently [3,4,5,6,7]. Utilized by this method, high-throughput and quantitative glycomics can be performed on various biological samples that include large amount of impurities
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