Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Neurosurgery, Lishui People's Hospital (The Sixth Affiliated Hospital of Wenzhou Medical University), Lishui, China.
Front Immunol. 2021 Apr 6;12:648416. doi: 10.3389/fimmu.2021.648416. eCollection 2021.
Previous research indicated that the tumor cells and microenvironment interactions are critical for the immunotherapeutic response. However, predicting the clinical response to immunotherapy remains a dilemma for clinicians. Hence, this study aimed to investigate the associations between expression and prognosis and tumor-infiltrating immune cells in glioma.
Firstly, we detected the expression in glioma tissues through biological databases. The chi-squared test, Kaplan-Meier, and univariate and multivariate Cox regression analyses were used to analyze the clinical significance of expression. The correlation between expression and levels of tumor-infiltrating immune cells in glioma tissues was investigated. Receiver operating characteristic (ROC) analysis was performed to compare the predictive power between and other commonly immune-related markers.
In the CGGA cohort of 325 glioma patients, we found that was upregulated in glioma, and increased with tumor grade. High expression was prominently associated with unfavorable clinicopathological features, and poorer survival of patients, which were further confirmed by TCGA (n=609) and GEO (n=74) cohorts. Furthermore, multivariate analysis indicated that is an independent prognostic biomarker for glioma. Importantly, overexpression was associated with a higher infiltration level of CD4 T cells, CD8 T cells, B cells, macrophages, and neutrophils in glioma. ROC curves showed that, compared with , , and , presented a higher area under the curve (AUC) value (AUC=0.824) for predicting high immune infiltration levels in glioma.
We found that was upregulated and could act as a poor prognostic biomarker in glioma. Importantly, overexpression was associated with the immune infiltration levels of immune cells including B cells, CD4 T cells, CD8 T cells, macrophages, and neutrophils, and strongly with the overall immune infiltration levels of glioma. These findings suggested that might be a potential biomarker for evaluating prognosis and immune infiltration in glioma.
先前的研究表明，肿瘤细胞与微环境的相互作用对免疫治疗反应至关重要。然而，预测免疫治疗的临床反应仍然是临床医生面临的难题。因此，本研究旨在探讨在胶质瘤中表达与预后和肿瘤浸润免疫细胞的关系。
首先，我们通过生物数据库检测胶质瘤组织中的表达。采用卡方检验、Kaplan-Meier 分析、单因素和多因素 Cox 回归分析来分析表达的临床意义。研究表达与胶质瘤组织中肿瘤浸润免疫细胞水平的相关性。采用接收者操作特征（ROC）分析比较与其他常见免疫相关标志物的预测能力。
在 CGGA 队列的 325 例胶质瘤患者中，我们发现在胶质瘤中上调，且随着肿瘤分级的增加而上调。高表达与不利的临床病理特征和患者预后不良显著相关，这在 TCGA（n=609）和 GEO（n=74）队列中得到进一步证实。此外，多因素分析表明是胶质瘤的独立预后生物标志物。重要的是，表达上调与胶质瘤中 CD4 T 细胞、CD8 T 细胞、B 细胞、巨噬细胞和中性粒细胞的浸润水平较高相关。ROC 曲线显示，与相比，、、和 ，在预测胶质瘤中高免疫浸润水平方面表现出更高的 AUC 值（AUC=0.824）。
我们发现在胶质瘤中上调，可作为预后不良的生物标志物。重要的是，表达上调与包括 B 细胞、CD4 T 细胞、CD8 T 细胞、巨噬细胞和中性粒细胞在内的免疫细胞浸润水平以及胶质瘤的整体免疫浸润水平密切相关。这些发现表明可能是评估胶质瘤预后和免疫浸润的潜在生物标志物。
