摘要
Abstract
Objective To establish the risk score prediction model of osteosarcoma prognosis based on cancer-associated fibroblasts(CAFs),and to analyze its relation with immune microenvironment.Methods Based on single cell RNA sequencing data of 6 patients with osteosarcoma in GSE162454 dataset,CAFs subsets were identified and differentially expressed genes(DEGs)in CAFs subsets were screened.For DEGs of CAFs,weighted gene co-expression network analysis was used for gene clustering,and cor function was used to screen immune genes of CAFs(IG_CAFs).The univariate and multivariate COX regression models and least absolute shrinkage and selection operator regression model were used to analyze genes independently correlated with the prognosis of patients with osteosarcoma to establish a risk score prediction model and evaluate its predictive performance.The xCell,MCPcounter and CIBERSORT algorithms were used to evaluate the correlation of risk score prediction model with level of immune cell infiltration.The qRT-PCR was used to analyze the expression of IG-CAFs in human osteoblasts(hFOB1.19)and osteosarcoma cell lines(143B,SA0S2,HOS and MG63).Results A total of 912 DEGs of CAFs were screened,and 6 IG_CAFs(BCAR1,BMP1,IFITM3,RGS5,SERPINE2 and TUSC1)were independently correlated genes with the prognosis of patients with osteosarcoma.The risk score prediction model was equal to(-0.120×BCAR1)+(0.039×BMP1)+(-0.005×IFITM3)+(-0.119×RGS5)+(0.013×SERPINE2)+(0.112×TUSC1).The prediction performance of risk score prediction model in test dataset and validation dataset was favorable.Among the three immune infiltration algorithms,there was a relatively strong correlation between the risk score prediction model and monocyte-macrophage system.Compared with hFOB1.19 cells,BCAR1,TUSC1,RGS5,BMP1,IFITM3 and SERPINE2 were differentially expressed in four categories of osteosarcoma cell lines.Conclusion The risk score prediction model established based on SERPINE2,BMP1,TUSC1,RGS5,IFITM3 and BCAR1 has a good prediction performance for the prognosis of patients with osteosarcoma.These 6 IG_CAFs may affect the immune microenvironment and the prognosis of patients by regulating monocyte-macrophages.关键词
肿瘤相关成纤维细胞/骨肉瘤/单细胞RNA测序/预后/风险评分预测模型/免疫浸润Key words
Cancer-associated fibroblasts/Osteosarcoma/Single cell RNA sequencing/Prognosis/Risk score prediction model/Immune infiltration分类
医药卫生
