Prognostically Significant Glycan Profiles of Clear Cell Renal Cell Carcinoma Identified by Integrated Glycome–Methylome Analysis

The aim of this study was to clarify the clinicopathological significance of the glycan profile of clear cell renal cell carcinoma (ccRCC). Comprehensive glycomic analysis and methylome analysis were performed using 50 paired nontumorous renal tissue (N) and tumorous tissue (T) specimens from patients with ccRCC. In comparison to N samples, T samples showed higher signal intensities for lectins recognizing high-mannose glycans and lower intensity for fucose and sialic acid, indicating that N-type glycans remain "immature" in ccRCCs. Hierarchical clustering using the signal intensities of lectins recognizing high-mannose glycans, fucose, and sialic acid divided T samples into Cluster A (n = 32) and Cluster B (n = 18). In Cluster B, the incidence of tumor-related death was higher (p = 0.017) and overall survival was lower (p = 0.019). Moreover, asialo-type glycans and N-acetyllactosamine residues, which are recognized by lectins DSA, ECA, and PHA-E, had an impact on both recurrence-free and overall survival. The expression of glycogenes, such as MGAT1, ST6GAL1, and TUSC3, may be epigenetically regulated. These results suggest that the glycan profile may be at least partly attributable to epigenetic regulation of glycogenes, and that comprehensive glycan profiling could provide clinically useful information for patients with ccRCC.