Rewiring of the N-Glycome with prostate cancer progression and therapy resistance

作者：William Butler, Colin T. McDowell, Qing Yang, Yiping He, Yue Zhao, J. Spencer Hauck, Yinglu Zhou, Hong Zhang, Andrew J. Armstrong, Daniel J. George, Richard R. Drake, Jiaoti Huang · 发表于：npj Precision Oncology · 年份：2023 · DOI：10.1038/s41698-023-00363-2 · 被引用次数：22 · 研究领域：Glycosylation and Glycoproteins Research、Mass Spectrometry Techniques and Applications、Prostate Cancer Treatment and Research

An understanding of the molecular features associated with prostate cancer progression (PCa) and resistance to hormonal therapy is crucial for the identification of new targets that can be utilized to treat advanced disease and prolong patient survival. The glycome, which encompasses all sugar polymers (glycans) synthesized by cells, has remained relatively unexplored in the context of advanced PCa despite the fact that glycans have great potential value as biomarkers and therapeutic targets due to their high density on the cell surface. Using imaging mass spectrometry (IMS), we profiled the N-linked glycans in tumor tissue derived from 131 patients representing the major disease states of PCa to identify glycosylation changes associated with loss of tumor cell differentiation, disease remission, therapy resistance and disease recurrence, as well as neuroendocrine (NE) differentiation which is a major mechanism for therapy failure. Our results indicate significant changes to the glycosylation patterns in various stages of PCa, notably a decrease in tri- and tetraantennary glycans correlating with disease remission, a subsequent increase in these structures with the transition to therapy-resistant PCa, and downregulation of complex N-glycans correlating with NE differentiation. Furthermore, both nonglucosylated and monoglucosylated mannose 9 demonstrate aberrant upregulation in therapy-resistant PCa which may be useful therapeutic targets as these structures are not normally p...