Zhang Qiang, Zhong Hua, Fan Yinchun, Liu Qian, Song Jiancheng, Yao Shengtao, Cao Fang
Department of Cerebrovascular Disease, Affiliated Hospital of Zunyi Medical University, Guizhou, China.
College of Life Sciences, Wuhan University, Wuhan, China.
Front Bioeng Biotechnol. 2020 Jun 30;8:592. doi: 10.3389/fbioe.2020.00592. eCollection 2020.
Immune checkpoints target regulatory pathways in T cells that enhance antitumor immune responses and elicit durable clinical responses. As a novel immune checkpoint, is an attractive key target for cancer immunotherapy. However, there has been no integrative investigation of in glioma. Our study explored the relationship between expression and clinical prognosis in glioma.
RNA and clinical data for a total of 1,001 samples were included in this study, including 325 samples from the Chinese Glioma Genome Atlas (CGGA) database and 676 samples from The Cancer Genome Atlas (TCGA) dataset. The R programming language was employed to perform statistical analysis and draw figures.
had a consistently positive relationship with glioblastoma and was highly enriched in IDH-wildtype and mesenchymal subtype glioma. Gene ontology enrichment and gene set variation analysis analyses suggested that was mostly involved in immune functions and was especially related to T cell-mediated immune response in glioma. Subsequent immune infiltration analysis showed that was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and DCs in glioblastoma multiforme and low-grade glioma. Additionally, was tightly associated with other immune checkpoints, including , , , and . Univariate and multivariate Cox analysis demonstrated that acts as an independent indicator of poor prognosis in glioma.
expression was increased in malignant phenotype and negatively associated with overall survival in glioma. also showed a positive correlation with other immune checkpoints, immune response, and inflammatory activity. Our findings indicate that is a promising clinical target for further immunotherapeutic use in glioma patients.
免疫检查点靶向T细胞中的调节通路,这些通路可增强抗肿瘤免疫反应并引发持久的临床反应。作为一种新型免疫检查点,是癌症免疫治疗中一个有吸引力的关键靶点。然而,尚未对其在胶质瘤中的情况进行综合研究。我们的研究探讨了其在胶质瘤中的表达与临床预后之间的关系。
本研究纳入了总共1001个样本的RNA和临床数据,其中包括来自中国胶质瘤基因组图谱(CGGA)数据库的325个样本和来自癌症基因组图谱(TCGA)数据集的676个样本。使用R编程语言进行统计分析并绘制图表。
与胶质母细胞瘤始终呈正相关,且在异柠檬酸脱氢酶(IDH)野生型和间充质亚型胶质瘤中高度富集。基因本体富集分析和基因集变异分析表明,主要参与免疫功能,尤其与胶质瘤中T细胞介导的免疫反应相关。随后的免疫浸润分析显示,在多形性胶质母细胞瘤和低级别胶质瘤中,与CD4 + T细胞、CD8 + T细胞、巨噬细胞、中性粒细胞和树突状细胞(DC)的浸润水平呈正相关。此外,与其他免疫检查点紧密相关,包括、、和。单因素和多因素Cox分析表明,在胶质瘤中是预后不良的独立指标。
在胶质瘤的恶性表型中表达增加,且与总生存期呈负相关。还与其他免疫检查点、免疫反应和炎症活性呈正相关。我们的研究结果表明,在胶质瘤患者中是进一步免疫治疗应用的一个有前景的临床靶点。