Association of glioma CD44 expression with glial dynamics in the tumour microenvironment and patient prognosis.
Association of glioma CD44 expression with glial dynamics in the tumour microenvironment and patient prognosis.
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DOI：
10.1016/j.csbj.2022.09.003
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发表时间：
2022
影响因子：
6
通讯作者：
Wang, Zhongxing
中科院分区：
文献类型：
--
作者：
Du, Zhanxin;Wang, Yaqing;Liang, Jiaqi;Gao, Shaowei;Cai, Xiaoying;Yu, Yu;Qi, Zhihui;Li, Jing;Xie, Yubin;Wang, Zhongxing
由于低级别胶质瘤(LGG)的异质性，患者表现出不同的生存结果，而组织学分类并不能可靠地预测这些结果。肿瘤微环境(TME)参与了脑部LGGs的发生和发展。根据TME中的免疫和间质成分识别潜在的预后标记物，将为LGG中TME的这两个成分的动态调节提供新的见解。我们应用Estimate来计算来自癌症基因组图谱数据库的免疫成分和基质成分的比率。在结合差异基因表达分析、蛋白质相互作用网络构建和生存分析后，CD44被筛选为一个独立的预后因素，并利用中国脑胶质瘤基因组图谱数据库的数据进行了验证。为了阐明胶质瘤细胞CD44的表达与TME中基质细胞和肿瘤进展的关系，采用RT-qPCR、细胞存活率和伤口愈合试验来确定星形胶质瘤细胞是否通过上调CD44的表达来促进胶质瘤细胞的存活和迁移。令人惊讶的是，Ciberort分析发现M1巨噬细胞与CD44的表达呈正相关。根据单细胞测序数据，进一步建议CD44+胶质瘤细胞通过骨桥蛋白信号与小胶质细胞来源的巨噬细胞(M1表型)相互作用。总体而言，我们发现星形胶质细胞可以提高胶质瘤细胞CD44的表达水平，促进M1巨噬细胞的募集，这可能通过骨桥蛋白-CD44信号促进胶质瘤的干化。因此，胶质瘤CD44的表达可能与TME内的胶质细胞活动相协调，可作为LGGs潜在的治疗靶点和预后标志物。
Because of the heterogeneity of lower-grade gliomas (LGGs), patients show various survival outcomes that are not reliably predicted by histological classification. The tumour microenvironment (TME) contributes to the initiation and progression of brain LGGs. Identifying potential prognostic markers based on the immune and stromal components in the TME will provide new insights into the dynamic modulation of these two components of the TME in LGGs. We applied ESTIMATE to calculate the ratio of immune and stromal components from The Cancer Genome Atlas database. After combined differential gene expression analysis, protein–protein interaction network construction and survival analysis, CD44 was screened as an independent prognostic factor and subsequently validated utilizing data from the Chinese Glioma Genome Atlas database. To decipher the association of glioma cell CD44 expression with stromal cells in the TME and tumour progression, RT–qPCR, cell viability and wound healing assays were employed to determine whether astrocytes enhance glioma cell viability and migration by upregulating CD44 expression. Surprisingly, M1 macrophages were identified as positively correlated with CD44 expression by CIBERSORT analysis. CD44+ glioma cells were further suggested to interact with microglia-derived macrophages (M1 phenotype) via osteopontin signalling on the basis of single-cell sequencing data. Overall, we found that astrocytes could elevate the CD44 expression level of glioma cells, enhancing the recruitment of M1 macrophages that may promote glioma stemness via osteopontin-CD44 signalling. Thus, glioma CD44 expression might coordinate with glial activities in the TME and serve as a potential therapeutic target and prognostic marker for LGGs.
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影响因子：
4.3
作者：
Bien-Möller S;Balz E;Herzog S;Plantera L;Vogelgesang S;Weitmann K;Seifert C;Fink MA;Marx S;Bialke A;Venugopal C;Singh SK;Hoffmann W;Rauch BH;Schroeder HWS
通讯作者：
Schroeder HWS
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
4.7
作者：
Carvalho, Joao
通讯作者：
Carvalho, Joao
影响因子：
5.1
作者：
Gudbergsson, Johann Mar;Christensen, Esben;Andresen, Thomas Lars
通讯作者：
Andresen, Thomas Lars
影响因子：
46.9
作者：
Gao R;Bai S;Henderson YC;Lin Y;Schalck A;Yan Y;Kumar T;Hu M;Sei E;Davis A;Wang F;Shaitelman SF;Wang JR;Chen K;Moulder S;Lai SY;Navin NE
通讯作者：
Navin NE