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PLCG2 作为软组织肉瘤肿瘤微环境重塑的潜在标志物。

PLCG2 as a potential indicator of tumor microenvironment remodeling in soft tissue sarcoma.

机构信息

Guangxi Medical University.

Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning.

出版信息

Medicine (Baltimore). 2021 Mar 19;100(11):e25008. doi: 10.1097/MD.0000000000025008.

Abstract

The tumor microenvironment (TME) plays an important role in the occurrence and development of soft tissue sarcoma (STS). A number of studies have shown that to inhibit tumor growth, the TME can be remodeled into an environment unsuitable for tumor proliferation. However, a lack of understanding exists regarding the dynamic regulation of TME.In this study, we used CIBERSORT and ESTIMATE calculation methods from the Cancer Genome Atlas (TCGA) database to calculate the proportion of tumor infiltrating immune cells (TICs) and the number of immune and stromal components in 263 STS samples. Differential expression genes (DEGs) shared by Immune Score and Stromal Score were obtained via difference analysis. Univariate Cox regression analysis and construction of protein-protein interaction (PPI) networks were applied to the DEGs.Through intersection analysis of univariate COX and PPI, PLCG2 was determined as the indicator. Further analysis showed that PLCG2 expression was positively correlated with the survival of STS patients. Gene set enrichment analysis (GSEA) showed that genes in the highly expressed PLCG2 group were enriched in immune-related activities. In the low-expression PLCG2 group, genes were enriched in the E2F, G2M, and MYC pathways. Difference analysis and correlation analysis showed that CD8+ T cells, gamma delta T cells, monocytes, and M1 macrophages were positively correlated with PLCG2 expression, indicating that PLCG2 may represent the immune status of TME.Therefore, the level of PLCG2 may aid in determining the prognosis of STS patients, especially the status of TME. These data provide additional insights into the remodeling of TME.

摘要

肿瘤微环境(TME)在软组织肉瘤(STS)的发生和发展中起着重要作用。许多研究表明,为了抑制肿瘤生长,可以将 TME 重塑为不利于肿瘤增殖的环境。然而,对于 TME 的动态调节仍缺乏了解。

在这项研究中,我们使用癌症基因组图谱(TCGA)数据库中的 CIBERSORT 和 ESTIMATE 计算方法,计算了 263 个 STS 样本中肿瘤浸润免疫细胞(TIC)的比例和免疫及基质成分的数量。通过差异分析获得了免疫评分和基质评分共享的差异表达基因(DEGs)。应用单因素 Cox 回归分析和蛋白质-蛋白质相互作用(PPI)网络构建对 DEGs 进行分析。

通过单因素 COX 和 PPI 的交集分析,确定 PLCG2 为指标。进一步分析表明,PLCG2 表达与 STS 患者的生存呈正相关。基因集富集分析(GSEA)显示,高表达 PLCG2 组的基因富集在免疫相关活性中。在低表达 PLCG2 组中,基因富集在 E2F、G2M 和 MYC 通路中。差异分析和相关性分析表明,CD8+T 细胞、γδT 细胞、单核细胞和 M1 巨噬细胞与 PLCG2 表达呈正相关,表明 PLCG2 可能代表 TME 的免疫状态。

因此,PLCG2 的水平可能有助于确定 STS 患者的预后,特别是 TME 的状态。这些数据为 TME 的重塑提供了更多的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446b/7982206/4a55f430329b/medi-100-e25008-g001.jpg

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