The tumor microenvironment (TME) has important effects on the tumorigenesis and development of osteosarcoma (OS). However, the dynamic mechanism regulating TME immune and matrix components remains unclear. In this study, we collected quantitative data on the gene expression of 88 OS samples from The Cancer Genome Atlas (TCGA) database and downloaded relevant clinical cases of OS from the TARGET database. The proportions of tumor-infiltrating immune cells (TICs) and the numbers of immune and matrix components were determined by CIBERSORT and ESTIMATE calculation methods. Protein-protein interaction (PPI) network construction and Cox regression analysis were conducted to analyze differentially expressed genes (DEGs). The complement components C1qA, C1qB and C1qC were then determined to be predictive factors through univariate Cox analysis and PPI cross analysis. Further analysis found that the levels of C1qA, C1qB and C1qC expression were positively linked to OS patient survival time and negatively correlated with the clinicopathological feature percent necrosis at definitive surgery. The results of gene set enrichment analysis (GSEA) demonstrated that genes related to immune functions were significantly enriched in the high C1qA, C1qB and C1qC expression groups. Proportion analysis of TICs by CIBERSORT showed that the levels of C1qA, C1qB and C1qC expression were positively related to M1 and M2 macrophages and CD8+ cells and negatively correlated with M0 macrophages. These results further support the influence of the levels of C1qA, C1qB and C1qC expression on the immune activity of the TME. Therefore, C1qA, C1qB and C1qC may be potential indicators of remodeling in the OS TME, which is helpful to predict the prognosis of patients with OS and provide new ideas for immunotherapy for OS.
Purpose
The aim of this work was to investigate the risk factors for cement leakage and new-onset OVCF after Percutaneous vertebroplasty (PVP) and to develop and validate a clinical prediction model (Nomogram).
Methods
Patients with Osteoporotic VCF (OVCF) treated with PVP at Liuzhou People’s Hospital from June 2016 to June 2018 were reviewed and met the inclusion criteria. Relevant data affecting bone cement leakage and new onset of OVCF were collected. Predictors were screened using univariate and multi-factor logistic analysis to construct Nomogram and web calculators. The consistency of the prediction models was assessed using calibration plots, and their predictive power was assessed by tenfold cross-validation. Clinical value was assessed using Decision curve analysis (DCA) and clinical impact plots.
Results
Higher BMI was associated with lower bone mineral density (BMD). Higher BMI, lower BMD, multiple vertebral fractures, no previous anti-osteoporosis treatment, and steroid use were independent risk factors for new vertebral fractures. Cement injection volume, time to surgery, and multiple vertebral fractures were risk factors for cement leakage after PVP. The development and validation of the Nomogram also demonstrated the predictive ability and clinical value of the model.
Conclusions
The established Nomogram and web calculator (https://dr-lee.shinyapps.io/RefractureApp/) (https://dr-lee.shinyapps.io/LeakageApp/) can effectively predict the occurrence of cement leakage and new OVCF after PVP.
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