Metabolic-related gene pairs signature analysis identifies ABCA1 expression levels on tumor-associated macrophages as a prognostic biomarker in primary IDHWT glioblastoma
文献类型：期刊论文
| 作者 | Wang, Shiqun2,3; Li, Lu4 ; Zuo, Shuguang1; Kong, Lingkai2; Wei, Jiwu2; Dong, Jie2
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| 刊名 | FRONTIERS IN IMMUNOLOGY
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| 出版日期 | 2022-09-30 |
| 卷号 | 13 |
| ISSN号 | 1664-3224 |
| 关键词 | primary glioblastoma wild-type isocitrate dehydrogenase metabolic-related gene pairs prognosis tumor-associated macrophages ABCA1 |
| DOI | 10.3389/fimmu.2022.869061 |
| 通讯作者 | Wei, Jiwu(wjw@nju.edu.cn) ; Dong, Jie(dongjie@nju.edu.cn) |
| 英文摘要 | Background: Although isocitrate dehydrogenase (IDH) mutation serves as a prognostic signature for routine clinical management of glioma, nearly 90% of glioblastomas (GBM) patients have a wild-type IDH genotype (IDHWT) and lack reliable signatures to identify distinct entities. Methods: To develop a robust prognostic signature for IDHWT GBM patients, we retrospectively analyzed 4 public datasets of 377 primary frozen tumor tissue transcriptome profiling and clinical follow-up data. Samples were divided into a training dataset (204 samples) and a validation (173 samples) dataset. A prognostic signature consisting of 21 metabolism-related gene pairs (MRGPs) was developed based on the relative ranking of single-sample gene expression levels. GSEA and immune subtype analyses were performed to reveal differences in biological processes between MRGP risk groups. The single-cell RNA-seq dataset was used to examine the expression distribution of each MRG constituting the signature in tumor tissue subsets. Finally, the association of MRGs with tumor progression was biologically validated in orthotopic GBM models. Results: The metabolic signature remained an independent prognostic factor (hazard ratio, 5.71 [3.542-9.218], P < 0.001) for stratifying patients into high- and low-risk levels in terms of overall survival across subgroups with MGMTp methylation statuses, expression subtypes, and chemo/ratio therapies. Immune-related biological processes were significantly different between MRGP risk groups. Compared with the low-risk group, the high-risk group was significantly enriched in humoral immune responses and phagocytosis processes, and had more monocyte infiltration and less activated DC, NK, and gamma delta T cell infiltration. scRNA-seq dataset analysis identified that the expression levels of 5 MRGs (ABCA1, HMOX1, MTHFD2, PIM1, and PTPRE) in TAMs increased with metabolic risk. With tumor progression, the expression level of ABCA1 in TAMs was positively correlated with the population of TAMs in tumor tissue. Downregulation of ABCA1 levels can promote TAM polarization towards an inflammatory phenotype and control tumor growth. Conclusions: The metabolic signature is expected to be used in the individualized management of primary IDHWT GBM patients. |
| WOS关键词 | GLIOMAS ; HETEROGENEITY ; TEMOZOLOMIDE ; VALIDATION ; SURVIVAL ; BENEFIT |
| 资助项目 | National Natural Science Foundation of China ; [82273261] ; [81773255] ; [81472820] |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| 出版者 | FRONTIERS MEDIA SA |
| WOS记录号 | WOS:000868634300001 |
| 资助机构 | National Natural Science Foundation of China |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/129402]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Wei, Jiwu; Dong, Jie |
| 作者单位 | 1.Guangxi Med Univ, Affiliated Liutie Cent Hosp, Liuzhou Key Lab Mol Diag, Guangxi Key Lab Mol Diag & Applicat, Liuzhou, Guangxi, Peoples R China 2.Nanjing Univ, Jiangsu Key Lab Mol Med, Med Sch, Nanjing, Jiangsu, Peoples R China 3.Univ Chinese Acad Sci, Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp,Inst Basic Med & Canc IBMC, Hangzhou, Zhejiang, Peoples R China 4.Zhejiang Univ, Dept Nephrol, Affiliated Childrens Hosp, Hangzhou, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Shiqun,Li, Lu,Zuo, Shuguang,et al. Metabolic-related gene pairs signature analysis identifies ABCA1 expression levels on tumor-associated macrophages as a prognostic biomarker in primary IDHWT glioblastoma[J]. FRONTIERS IN IMMUNOLOGY,2022,13. |
| APA | Wang, Shiqun,Li, Lu,Zuo, Shuguang,Kong, Lingkai,Wei, Jiwu,&Dong, Jie.(2022).Metabolic-related gene pairs signature analysis identifies ABCA1 expression levels on tumor-associated macrophages as a prognostic biomarker in primary IDHWT glioblastoma.FRONTIERS IN IMMUNOLOGY,13. |
| MLA | Wang, Shiqun,et al."Metabolic-related gene pairs signature analysis identifies ABCA1 expression levels on tumor-associated macrophages as a prognostic biomarker in primary IDHWT glioblastoma".FRONTIERS IN IMMUNOLOGY 13(2022). |
入库方式： OAI收割
来源：合肥物质科学研究院
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