Single-cell dissection of PTM-related networks reveals an immunosuppressed osteosarcoma ecosystem

作者：Jingyu Chen, Wei Zhang, Hai Yan, Jinyu Chen, Hanrui Liu, Xingyu Zhou, Haiping Zhang, Dongdong Cheng · 发表于：Frontiers in Molecular Biosciences · 年份：2025 · DOI：10.3389/fmolb.2025.1718941 · 被引用次数：1 · 研究领域：Single-cell and spatial transcriptomics、MicroRNA in disease regulation、Cancer Cells and Metastasis

Background Osteosarcoma remains lethal for many patients with metastatic or relapsed disease. Post-translational modifications (PTMs) regulate protein signaling and may shape the tumor microenvironment and clinical behavior in osteosarcoma, but PTM-anchored transcriptomic programs are as yet not well defined. Methods We integrated single-cell RNA sequencing from GSE162454 with curated PTM and immune gene sets to build a PTM-related framework for osteosarcoma. Tumor cell differentially expressed genes were intersected with PTM and immune repertoires to derive candidates. A PTM-related prognostic score was trained in TARGET-OS and validated in GSE21257 and GSE16091. Immune infiltration and microenvironment features were profiled using ssGSEA, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression (ESTIMATE) data, and Tumor Immune Dysfunction and Exclusion (TIDE) scores. Model interpretation used SHapley Additive exPlanations (SHAP) and single-cell localization. GRN was prioritized for exploration of immune correlations and in vitro loss-of-function assays in U2OS and HOS cells. Results The three-way intersection yielded 298 genes. The PTM-related score stratified overall survival in training and validation cohorts and remained independent of clinical covariates. High scores aligned with an immunosuppressed, stroma-rich microenvironment, with lower ImmuneScores and ESTIMATE scores, enrichment of myeloid and regulatory lineages, higher dysfunction and ...