Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma

Autor: Dongan He, Xiaoqian Che, Haiming Zhang, Jiandong Guo, Lei Cai, Jian Li, Jinxi Zhang, Xin Jin, Jianfeng Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Discover Oncology, Vol 15, Iss 1, Pp 1-17 (2024)
Druh dokumentu: article
ISSN: 2730-6011
DOI: 10.1007/s12672-024-01523-x
Popis: Abstract Osteosarcoma (OSA) is a primary bone malignancy characterized by its aggressive nature and high propensity for metastasis. Despite advancements in multimodal therapies, the clinical outcomes for OSA patients remain suboptimal, necessitating deeper molecular insights for improved therapeutic strategies. Here, we employed single-cell RNA sequencing (scRNA-seq) to elucidate the cellular heterogeneity and transcriptional dynamics of OSA tumors. Our study identified eleven distinct tumor cell subpopulations, including osteoblastic, chondroblastic, and myeloid lineages, each exhibiting unique transcriptional profiles associated with disease progression and metastasis. Epithelial-mesenchymal transition (EMT) emerged as a critical process driving aggressive phenotypes, supported by gene set enrichment analyses (GSVA) and transcription factor regulatory network analyses. Integration of copy number variation (CNV) data highlighted genomic alterations in osteoblastic and chondroblastic cells, implicating potential therapeutic targets. Furthermore, immune cell infiltration analyses revealed distinct immune profiles across OSA subtypes, correlating with tumor mutational burden (TMB) and clinical outcomes. Our findings underscore the complexity of OSA biology and provide a foundation for developing personalized treatment strategies targeting tumor heterogeneity and immune interactions.
Databáze: Directory of Open Access Journals