Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma.
Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma.
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DOI：
10.3389/fonc.2021.642144
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhou HH
中科院分区：
文献类型：
--
作者：
Chen LH;Liu JF;Lu Y;He XY;Zhang C;Zhou HH
肿瘤微环境（TME）在骨肉瘤（OS）的发生、发展中起重要作用。然而，调节TME免疫和基质成分的动态机制仍不清楚。在这项研究中，我们从癌症基因组图谱（TCGA）数据库中收集了88个OS样本的基因表达定量数据，并从TARGET数据库中下载了OS的相关临床病例。采用CIBERSORT和ESTIMATE计算方法测定肿瘤浸润免疫细胞（TIC）的比例以及免疫和基质成分的数量。构建蛋白质相互作用（PPI）网络，采用考克斯回归分析差异表达基因（DEG）。通过单因素考克斯分析和PPI交叉分析确定补体成分C1qA、C1qB和C1qC为预测因子。进一步分析发现，C1qA、C1qB和C1qC表达水平与OS患者生存时间呈正相关，与确定性手术时的临床病理特征坏死百分比呈负相关。基因集富集分析（GSEA）结果表明，C1qA、C1qB和C1qC高表达组中与免疫功能相关的基因显著富集。CIBERSORT法分析TIC细胞比例发现，C1qA、C1qB和C1qC表达水平与M1、M2巨噬细胞和CD8+细胞呈正相关，与M0巨噬细胞呈负相关。这些结果进一步支持C1qA、C1qB和C1qC表达水平对TME免疫活性的影响。因此，C1qA、C1qB和C1qC可能是OS TME重构的潜在指标，有助于预测OS患者的预后，并为OS的免疫治疗提供新的思路。
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.
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影响因子：
7.3
作者：
Agostinis C;Vidergar R;Belmonte B;Mangogna A;Amadio L;Geri P;Borelli V;Zanconati F;Tedesco F;Confalonieri M;Tripodo C;Kishore U;Bulla R
通讯作者：
Bulla R
DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
通讯作者：
Marini FC
影响因子：
3.7
作者：
Hong Q;Sze CI;Lin SR;Lee MH;He RY;Schultz L;Chang JY;Chen SJ;Boackle RJ;Hsu LJ;Chang NS
通讯作者：
Chang NS
影响因子：
45.3
作者：
Robbins, Paul F.;Morgan, Richard A.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
11.5
作者：
Khanna, Chand;Fan, Timothy M.;Bernstein, Mark
通讯作者：
Bernstein, Mark