A molecular landscape and prognosis signature based on histone tyrosine sulfation in pan‐cancer analysis

作者：Meijuan Cai, Yuhao Liao, Jun Lin, Xumeng Chen, Yi-Xiang Wang, Zhijuan Li, Zhengjun Yang, Diankui Cai · 发表于：Clinical and Translational Discovery · 年份：2026 · DOI：10.1002/ctd2.70178 · 研究领域：Ferroptosis and cancer prognosis、Epigenetics and DNA Methylation、Immune cells in cancer

Abstract Background Tyrosine sulfation, a widespread post‐translational modification in mammals mainly associated with secretory and transmembrane proteins, has recently been found to occur on histones. However, the molecular landscape and prognostic signature of pan‐cancer based on histone tyrosine sulfation ( HYsulf ) remain poorly understood. Methods We investigated the expression diversity, molecular regulation landscape, DNA methylation and mutation patterns of 51 HYsulf ‐related genes across 33 cancer types from the Cancer Genome Atlas (TCGA). Additionally, we classified pan‐cancer samples into high‐ and low‐score subgroups (Hscore and Lscore) by establishing the HYsulf score. Result Enrichment analysis revealed high enrichment of immune‐related pathways, cancer‐associated hallmarks and pathways, hypoxia, metabolism and cell fate‐related pathways in the Hscore subgroup. Infiltration analysis indicated correlations between immune infiltration and HYsulf score, with negative associations observed primarily with activated and resting NK cells, while positive correlations were prominent with Tregs, macrophages M1 and M0. HYsulf score showed significant correlations with immuno‐inhibitors, immuno‐stimulators, MHC, chemokines and their receptors, as well as emerging biomarkers of immune therapeutic response such as TMB, MSI and neoantigens. Furthermore, evaluations of seven metabolic features suggested a strong link between HYsulf and metabolic reprogramming in pan‐cancer. Ad...