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Updated: Jun 19, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Multi-omics Analysis of Histone-related Genes in Osteosarcoma: A Multidimensional Integrated Study Revealing Drug
Yang Yang1, Xinqiao Tang1, Zhong Liu2
1Department of Orthopedic Surgery, Xiangtan Central Hospital, Xiangtan, Hunan, P.R. China.
Abstract:
IntroductionOsteosarcoma (OS) is a highly aggressive primary bone malignancy with poor prognosis. Histone modifications play crucial roles in tumor progression, but their systematic investigation in OS remains unexplored.MethodsThis study integrated single-cell RNA sequencing data and large-scale clinical information to systematically analyze the spatial heterogeneity of histone modifications in OS and their clinical significance. We employed Seurat for single-cell data analysis, CellChat for cell-cell communication network analysis, and LASSO Cox regression to construct a prognostic model. Additionally, we conducted functional enrichment analysis, immune characteristics analysis, and drug sensitivity prediction.ResultsWe identified five major cell types in the OS microenvironment and discovered significant differences in histone modification levels among different cell types, with osteosarcoma cells and endothelial cells exhibiting higher modification levels. Cell-cell communication network analysis revealed the importance of signaling pathways such as SPP1, CypA, MIF, IGFBP, and VEGF in OS. Based on nine histone modification-related genes, we constructed an efficient prognostic model (AUC values of 0.713, 0.845, and 0.888 for 1-, 3-, and 5-year predictions, respectively), which was validated in an external cohort (AUC = 0.808). Immune microenvironment analysis showed significantly higher proportions of CD8+ T cells and Treg cells in the low-risk group. Drug sensitivity analysis revealed that the low-risk group was more sensitive to Imatinib, Rapamycin, and Sunitinib, while the high-risk group was more sensitive to MAPK pathway inhibitors.ConclusionThis study systematically revealed the spatial heterogeneity of histone modifications in OS and their clinical significance for the first time, proposing an "epigenetic-immune" regulatory network hypothesis and developing a histone modification-based prognostic model. Our proposed "epigenetic-guided personalized medication strategy" provides new insights for precision treatment of OS, potentially significantly improving patient prognosis.
Insights
This study reveals spatial differences in histone modifications within osteosarcoma (OS) and develops a predictive model for patient outcomes. Findings support an epigenetic-immune strategy for personalized OS treatment.
Area of Science:
- Oncology
- Epigenetics
- Genomics
Background:
- Osteosarcoma (OS) is an aggressive bone cancer with poor prognosis.
- Histone modifications are critical in cancer but their role in OS is understudied.
- Understanding OS heterogeneity is key for targeted therapies.
Purpose of the Study:
- To systematically analyze spatial heterogeneity of histone modifications in OS.
- To investigate the clinical significance of these modifications.
- To develop a prognostic model and explore therapeutic strategies.
Main Methods:
- Integrated single-cell RNA sequencing and clinical data.
- Utilized Seurat, CellChat, and LASSO Cox regression.
- Performed functional enrichment, immune analysis, and drug sensitivity prediction.
Main Results:
- Identified distinct histone modification levels across OS cell types.
- Constructed a validated prognostic model based on nine histone modification genes (AUCs up to 0.888).
- Linked low-risk groups to specific immune cells and drug sensitivities (Imatinib, Rapamycin, Sunitinib).
Conclusions:
- First systematic revelation of histone modification heterogeneity in OS and its clinical impact.
- Proposed an 'epigenetic-immune' regulatory network hypothesis.
- Developed a histone modification-based prognostic model for precision medicine in OS.
