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基于免疫相关基因的胶质瘤预后模型的开发

Development of a prognostic model of glioma based on immune-related genes.

作者信息

Wang Jing-Jing, Wang Han, Zhu Bao-Long, Wang Xiang, Qian Yong-Hong, Xie Lei, Wang Wen-Jie, Zhu Jie, Chen Xing-Yu, Wang Jing-Mei, Ding Zhi-Liang

机构信息

Department of Oncology, Taizhou Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu 225300, P.R. China.

Department of Oncology, Jining Cancer Hospital, Jining, Shandong 272000, P.R. China.

出版信息

Oncol Lett. 2021 Feb;21(2):116. doi: 10.3892/ol.2020.12377. Epub 2020 Dec 15.

Abstract

Glioma is the most common type of primary brain cancer, and the prognosis of most patients with glioma, and particularly that of patients with glioblastoma, is poor. Tumor immunity serves an important role in the development of glioma. However, immunotherapy for glioma has not been completely successful, and thus, comprehensive examination of the immune-related genes (IRGs) of glioma is required. In the present study, differentially expressed genes (DEGs) and differentially expressed IRGs (DEIRGs) were identified using the edgeR package. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used for functional enrichment analysis of DEIRGs. Survival-associated IRGs were selected via univariate Cox regression analysis. A The Cancer Genome Atlas prognostic model and GSE43378 validation model were established using lasso-penalized Cox regression analysis. Based on the median risk score value, patients were divided into high-risk and low-risk groups for clinical analysis. Receiver operating characteristic curve and nomogram analyses were used to assess the accuracy of the models. Reverse transcription-quantitative PCR was performed to measure the expression levels of relevant genes, such as cyclin-dependent kinase 4 (CDK4), interleukin 24 (IL24), NADPH oxidase 4 (NOX4), bone morphogenetic protein 2 (BMP2) and baculoviral IAP repeat containing 5 (BIRC5). A total of 3,238 DEGs, including 1,950 upregulated and 1,288 downregulated DEGs, and 97 DEIRGs, including 60 upregulated and 37 downregulated DEIRGs, were identified. 'Neuroactive ligand-receptor interaction' and 'Cytokine-cytokine receptor interaction' were the most significantly enriched pathways according to KEGG pathway analysis. A prognostic model and a validation prognostic model were created for glioma, including 15 survival-associated IRGs (FCER1G, NOX4, TRIM5, SOCS1, APOBEC3C, BIRC5, VIM, TNC, BMP2, CMTM3, IL24, JAG1, CALCRL, HNF4G and CDK4). Furthermore, multivariate Cox regression analysis results suggested that age, high WHO Grade by histopathology, wild type isocitrate dehydrogenase 1 and high risk score were independently associated with poor overall survival. The infiltration of B cells, CD8 T cells, dendritic cells, macrophages and neutrophils was positively associated with the prognostic risk score. In the present study, several clinically significant survival-associated IRGs were identified, and a prognosis evaluation model of glioma was established.

摘要

胶质瘤是最常见的原发性脑癌类型,大多数胶质瘤患者,尤其是胶质母细胞瘤患者的预后较差。肿瘤免疫在胶质瘤的发生发展中起重要作用。然而,胶质瘤的免疫治疗尚未完全成功,因此,需要对胶质瘤的免疫相关基因(IRGs)进行全面检查。在本研究中,使用edgeR软件包鉴定差异表达基因(DEGs)和差异表达免疫相关基因(DEIRGs)。采用京都基因与基因组百科全书(KEGG)通路分析对DEIRGs进行功能富集分析。通过单变量Cox回归分析选择生存相关IRGs。使用套索惩罚Cox回归分析建立癌症基因组图谱预后模型和GSE43378验证模型。根据中位风险评分值,将患者分为高风险和低风险组进行临床分析。采用受试者工作特征曲线和列线图分析评估模型的准确性。进行逆转录定量PCR以测量相关基因的表达水平,如细胞周期蛋白依赖性激酶4(CDK4)、白细胞介素24(IL24)、NADPH氧化酶4(NOX4)、骨形态发生蛋白2(BMP2)和含杆状病毒IAP重复序列5(BIRC5)。共鉴定出3238个DEGs,包括1950个上调DEGs和1288个下调DEGs,以及97个DEIRGs,包括60个上调DEIRGs和37个下调DEIRGs。根据KEGG通路分析,“神经活性配体-受体相互作用”和“细胞因子-细胞因子受体相互作用”是最显著富集的通路。建立了胶质瘤的预后模型和验证预后模型,包括15个生存相关IRGs(FCER1G、NOX4、TRIM5、SOCS1、APOBEC3C、BIRC5、VIM、TNC、BMP2、CMTM3、IL24、JAG1、CALCRL、HNF4G和CDK4)。此外,多变量Cox回归分析结果表明,年龄、组织病理学WHO分级高、异柠檬酸脱氢酶1野生型和高风险评分与总体生存不良独立相关。B细胞、CD8 T细胞、树突状细胞、巨噬细胞和中性粒细胞的浸润与预后风险评分呈正相关。在本研究中,鉴定了几个具有临床意义的生存相关IRGs,并建立了胶质瘤的预后评估模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cec2/7751470/fd831253694b/ol-21-02-12377-g01.jpg

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