胶质瘤
生物
间质细胞
癌症研究
巨噬细胞极化
流式细胞术
川地163
免疫组织化学
M2巨噬细胞
肿瘤进展
免疫系统
肿瘤微环境
基因
分子生物学
免疫学
遗传学
表型
肿瘤细胞
作者
Xiaobin Zhang,Xiaolin Sun,Guo Chen,Jianan Li,Guobiao Liang
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:2023-11-20
标识
DOI:10.1152/ajpcell.00234.2023
摘要
We elucidated the molecular mechanism of Cancer-associated fibroblasts (CAF)-associated gene IGFBP2-induced M2 macrophage polarization in the tumor microenvironment involved in glioma progression. TCGA and CGGA provided bulk RNA-seq datasets, ESTIMATE scores for glioma stromal cells, and OS-clinicopathological correlation analyses. TIMER provided CAF abundance in the TCGA glioma-related dataset, differential gene analysis was performed for high and low CAF groups, and weighted gene co-expression network analysis (WGCNA) identified CAF-related genes. Univariate and multifactorial COX regression analyses created CAF risk models. ssGSEA, CIBERSORT, GSE84465. Implanted glioma mice finished. Western blot and RT-qPCR showed IGFBP2 in tumor tissues. AAV decreased IGFBP2, flow cytometry measured M1 and M2 macrophage ratios, and immunohistochemistry detected markers. TCGA and CGGA transcriptome data showed malignant gliomas had higher stromal cell scores and worse prognoses. Low- and high-CAF TCGA gliomas. Differential expression, WGCNA, and multifactorial COX identified 132 CAF-related genes and 7 high-risk genes (CPQ, EFEMP2, IGFBP2, RAB42, TNFRSF12A, VASN). Neither CAF risk score, Grade, nor 1p/19q affected glioma prognosis. CAF only enriched EFEMP2 and IGFBP2. GEPIA compared EFEMP2 and IGFBP2 expression in normal brain tissue and gliomas. LGG and GBM highly expressed IGFBP2 and EFEMP2. GSEA raised IGFBP2. CIBERSORT linked M2 macrophage infiltration to TCGA glioma immune cell subpopulation IGFBP2 expression. IGFBP2 knockdown stopped mouse glioma and M2 macrophage polarization. CAF plays a pro-carcinogenic role in glioma, and the CAF-related gene IGFBP2 could promote glioma progression by inducing M2 macrophage polarization.
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