Department of Oral and Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, China.
Biomolecules. 2023 Feb 8;13(2):327. doi: 10.3390/biom13020327.
Osteosarcoma (OS) is the most common malignant bone tumor. However, treatment strategies have not changed over the past 30 years. The relationship between OS and the immune microenvironment may provide a basis for the establishment of novel therapeutic targets. In this study, a large-scale gene expression dataset (GSE42352) was used to identify key genes in OS. A Target-OS dataset from the Cancer Genome Atlas was used as a validation set. Ecotropic viral integration site 2B () was significantly upregulated in OS tumor samples. Differentially expressed genes (DEGs) were identified between samples with high and low expression in both the test and validation cohorts. The top three functions of DEGs determined by a gene set enrichment analysis (GSEA) were chemokine signaling, cytokine-cytokine receptor interaction, and Human T-cell leukemia virus 1 infection. A prognostic prediction model including , , and was constructed by a Cox regression analysis. This model indicated that is an independent protective prognostic marker in OS. An analysis of immune infiltration further showed that high expression levels were correlated with high levels of macrophage infiltration. Protein expression data derived from the Human Protein Atlas suggested to be highly expressed in monocytes. Finally, we validated the elevated expression of in OS cell lines and OS tissue samples; these results were consistent with those of the analyses of the GSE42352 and Target-OS datasets. Our integrative bioinformatics analysis and experimental results provide clear evidence for the prognostic value of in OS and its close relationship with monocyte and macrophage infiltration.
骨肉瘤(OS)是最常见的恶性骨肿瘤。然而,过去 30 年来,治疗策略并没有改变。OS 与免疫微环境之间的关系可能为建立新的治疗靶点提供依据。本研究利用大规模基因表达数据集(GSE42352)鉴定 OS 中的关键基因。使用癌症基因组图谱中的 Target-OS 数据集作为验证集。在 OS 肿瘤样本中,嗜碱性病毒整合位点 2B () 显著上调。在测试和验证队列中,均鉴定出 高表达和低表达样本之间的差异表达基因(DEGs)。基因集富集分析(GSEA)确定的 DEGs 的前三个功能是趋化因子信号、细胞因子-细胞因子受体相互作用和人 T 细胞白血病病毒 1 感染。通过 Cox 回归分析构建了包含 、 和 的预后预测模型。该模型表明 是 OS 中的独立保护性预后标志物。免疫浸润分析进一步表明,高 表达水平与巨噬细胞浸润水平高相关。人类蛋白质图谱得出的蛋白表达数据表明 在单核细胞中高表达。最后,我们验证了 在 OS 细胞系和 OS 组织样本中的高表达,这些结果与 GSE42352 和 Target-OS 数据集的分析结果一致。我们的综合生物信息学分析和实验结果为 在 OS 中的预后价值及其与单核细胞和巨噬细胞浸润的密切关系提供了明确的证据。