He Dongan, Che Xiaoqian, Zhang Haiming, Guo Jiandong, Cai Lei, Li Jian, Zhang Jinxi, Jin Xin, Wang Jianfeng
Department of Orthopaedics, Hangzhou Ninth People's Hospital, Hangzhou, China.
Discov Oncol. 2024 Nov 18;15(1):669. doi: 10.1007/s12672-024-01523-x.
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.
骨肉瘤（OSA）是一种原发性骨恶性肿瘤，其特点是具有侵袭性且转移倾向高。尽管多模式治疗取得了进展，但OSA患者的临床结局仍不尽人意，因此需要更深入的分子见解来改进治疗策略。在此，我们采用单细胞RNA测序（scRNA-seq）来阐明OSA肿瘤的细胞异质性和转录动态。我们的研究确定了11个不同的肿瘤细胞亚群，包括成骨细胞、软骨细胞和髓系谱系，每个亚群都表现出与疾病进展和转移相关的独特转录谱。基因集富集分析（GSVA）和转录因子调控网络分析表明，上皮-间质转化（EMT）是驱动侵袭性表型的关键过程。拷贝数变异（CNV）数据的整合突出了成骨细胞和软骨细胞中的基因组改变，提示了潜在的治疗靶点。此外，免疫细胞浸润分析揭示了OSA各亚型不同的免疫谱，与肿瘤突变负荷（TMB）和临床结局相关。我们的研究结果强调了OSA生物学的复杂性，并为制定针对肿瘤异质性和免疫相互作用的个性化治疗策略奠定了基础。
