Frontiers in immunology
GlycoRNA-related cellular program scoring identifies Siglec- and myeloid-associated tumor microenvironments for glycoRNA validation
By Kong M, Guan X, Jing Y and 5 others.
Abstract
Background
Glycosylated RNAs (glycoRNAs) represent a recently recognized connection between RNA biology and cell-surface glycobiology. However, whether glycoRNA-related processes are relevant to human tumors remains unclear, partly because direct glycoRNA measurements are not yet available across large cancer cohorts. We therefore used transcriptomic data to identify tumor settings in which glycoRNA-related programs may be most suitable for further experimental validation.
Methods
We curated a glycoRNA-focused literature evidence base and manually reviewed the top extracted relations to define gene modules related to RNA identity, N-glycan and sialylation pathways, RNA trafficking, and lectin/Siglec recognition. The glycoRNA-related cellular program score is an expression-based composite score representing coordinated glycoRNA-related cellular programs, including RNA processing, glycan biosynthesis, trafficking, and lectin/Siglec recognition. It is designed to prioritize tumor contexts for experimental glycoRNA validation. The score was applied to 9,186 TCGA tumors from 32 cancer types and analyzed together with clinical variables, leukocyte fraction, immune signatures, Siglec/checkpoint/myeloid-axis scores, and non-overlapping sensitivity models. Glioblastoma single-cell and spatial transcriptomic datasets were used for additional context-level validation.