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Abstract 5702: Cancer-specific glycosylation regulated by epigenomic alteration in renal cell carcinoma


 Background and Aims: Cancer-specific glycosylation plays an important role in the development and progression of cancer. Epigenetics may contribute to forming cancer-specific glycosylation by regulating the expression of glycogenes. Although comprehensive analysis of epigenetics is routinely performed, comprehensive glycan analysis, especially using human clinical samples, has been limited due to technical underdevelopment. Our aims are to understand the significance of glycosylation and its epigenetic regulation on renal carcinogenesis and to identify cancer-specific glycosylation as a potential diagnostic marker and a novel therapeutic target.
 Materials and Methods: Comprehensive glycomics and methylome analysis were performed by lectin microarray and Infinium HumanMethylation450 BeadChip on 50 non-cancerous renal cortex tissue (N) and 50 clear cell renal cell carcinoma (RCC) (T) microdissected from formalin-fixed and paraffin-embedded tissue samples.
 Results: Compared to N samples, T samples showed higher fluorescence intensity for lectins recognizing mannose-type glycans, and lower intensity for lectins recognizing sialyl and fucosyl groups. In RCC, the metabolism of N-glycans may remain in an immature state. By hierarchical clustering using lectin microarray data, T samples were divided into Clusters A and B with significant differences in patients’ outcome. Increased high-mannose type N-glycan and core fucosylation and decreased sialylation were observed in T samples of Cluster A. According to these results, glycosylation profiles showed heterogeneity associated with patients’ outcome among RCCs, and immature N-glycan may be specific in some RCCs. Methylome analysis suggests that specific glycosylation profiles of RCCs may be induced by DNA methylation alteration on glycogenes. Association between DNA methylation and mRNA expression was confirmed on some glycogenes using real-time reverse transcription PCR. As a result of examining whether the signal intensity pattern of each lectin reflects the prognosis of clear cell RCC, we could identify the lectins that reflect the RCCs prognosis.
 Conclusion: In RCC, the metabolism of N-glycans may remain in an immature state. The glycan profiles show heterogeneity among individual RCCs, and some of the specific glycan profiles may be associated with patients’ outcome. Cancer-specific glycan profiles may be regulated by epigenetic alteration of glycogenes.
 Citation Format: Yoshiko Kitazume, Eri Arai, Atsushi Matsuda, Kentaro Ohara, Akiko Miyagi Maeshima, Teruhiko Yoshida, Atsushi Kuno, Yae Kanai. Cancer-specific glycosylation regulated by epigenomic alteration in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5702.