Jiang Haoli, Du Haoyuan, Liu Yingnan, Tian Xiao, Xia Jinquan, Yang Shucai
Department of Orthopaedics, the Third People's Hospital of Shenzhen, Shenzhen, China.
Department of Orthopaedics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University & the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
Transl Cancer Res. 2022 Oct;11(10):3841-3852. doi: 10.21037/tcr-22-2370.
Mesenchymal stem cells (MSCs) play a crucial role in osteosarcoma (OS) growth and progression. This study conducted a bioinformatics analysis of a single-cell ribonucleic acid sequencing data set and explored the MSC-specific differentially expressed genes (DEGs) in advanced OS.
MSC-specific DEGs from GSE152048 was extracted using Seurat R package. These DEGs were then subjected to the functional analysis, and several key genes were further identified and underwent a prognosis analysis.
A total of 234 upregulated and 280 downregulated DEGs were identified between the MSCs and other cells, and a total of 188 upregulated and 158 downregulated DEGs were identified between the MSCs and osteoblastic cells. The Gene Ontology (GO) functional analysis showed that the specific DEGs between the MSCs and osteoblastic cells were enriched in GO terms such as "collagen catabolic process", "positive regulation of pathway-restricted SMAD protein phosphorylation", "osteoblast differentiation", "regulation of release of cytochrome c from mitochondria" and "interleukin-1 production". The specific DEGs between the MSCs and osteoblastic cells were subjected to a protein-protein interaction network analysis. Further, a survival analysis of 20 genes with combined scores >0.94 revealed that the low expression of () and () was associated with the shorter overall survival of OS patients, while the high expression of (), (), (), , and () was associated with the shorter overall survival of OS patients. In a further analysis, we compared the expression of , , , , , , and between the MSCs and high-grade OS cells. Further validation studies using the GSE42352 data set revealed that , , , and were more upregulated in the MSCs than the high-grade OS cells, while , , and were more downregulated in the MSCs than the high-grade OS cells.
Our bioinformatics analysis revealed 7 hub genes derived from the specific DEGs between the MSCs and osteoblastic cells. The 7 hub genes may serve as potential prognostic biomarkers for patients with OS.
间充质干细胞（MSCs）在骨肉瘤（OS）的生长和进展中起关键作用。本研究对单细胞核糖核酸测序数据集进行了生物信息学分析，并探索了晚期OS中MSCs特异性差异表达基因（DEGs）。
使用Seurat R包从GSE152048中提取MSCs特异性DEGs。然后对这些DEGs进行功能分析，进一步鉴定几个关键基因并进行预后分析。
在MSCs与其他细胞之间共鉴定出234个上调和280个下调的DEGs，在MSCs与成骨细胞之间共鉴定出188个上调和158个下调的DEGs。基因本体论（GO）功能分析表明，MSCs与成骨细胞之间的特异性DEGs在“胶原蛋白分解代谢过程”、“途径受限的SMAD蛋白磷酸化的正调控”、“成骨细胞分化”、“线粒体细胞色素c释放的调控”和“白细胞介素-1产生”等GO术语中富集。对MSCs与成骨细胞之间的特异性DEGs进行蛋白质-蛋白质相互作用网络分析。此外，对综合评分>0.94的20个基因进行生存分析，结果显示（）和（）的低表达与OS患者较短的总生存期相关，而（）、（）、（）、和（）的高表达与OS患者较短的总生存期相关。在进一步分析中，我们比较了MSCs与高级别OS细胞之间、、、、、、和的表达。使用GSE42352数据集进行的进一步验证研究表明，与高级别OS细胞相比，、、、在MSCs中上调更明显，而、、在MSCs中下调更明显。
我们的生物信息学分析揭示了7个源自MSCs与成骨细胞之间特异性DEGs的枢纽基因。这7个枢纽基因可能作为OS患者潜在的预后生物标志物。
