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解码免疫微环境:揭示CD8 + T细胞相关生物标志物并开发用于个性化胶质瘤治疗的预后特征。

Decoding the immune microenvironment: unveiling CD8 + T cell-related biomarkers and developing a prognostic signature for personalized glioma treatment.

作者信息

Lin Xiaofang, Liu Jianqiang, Zhang Ni, Zhou Dexiang, Liu Yakang

机构信息

Laboratory Department of Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Department of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan 2nd Road, Guangzhou, 510080, China.

出版信息

Cancer Cell Int. 2024 Oct 1;24(1):331. doi: 10.1186/s12935-024-03517-9.

Abstract

BACKGROUND

Gliomas are aggressive brain tumors with poor prognosis. Understanding the tumor immune microenvironment (TIME) in gliomas is essential for developing effective immunotherapies. This study aimed to identify TIME-related biomarkers in glioma using bioinformatic analysis of RNA-seq data.

METHODS

In this study, we employed weighted gene co-expression network analysis (WGCNA) on bulk RNA-seq data to identify TIME-related genes. To identify prognostic genes, we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Based on these genes, we constructed a prognostic signature and delineated risk groups. To validate the prognostic signature, external validation was conducted.

RESULTS

CD8 + T cell infiltration was strongly correlated with glioma patient prognosis. We identified 115 CD8 + T cell-related genes through integrative analysis of bulk-seq data. CDCA5, KIF11, and KIF4A were found to be significant immune-related genes (IRGs) associated with overall survival in glioma patients and served as independent prognostic factors. We developed a prognostic nomogram that incorporated these genes, age, gender, and grade, providing a reliable tool for clinicians to predict patient survival probabilities. The nomogram's predictions were supported by calibration plots, further validating its accuracy.

CONCLUSION

In conclusion, our study identifies CD8 + T cell infiltration as a strong predictor of glioma patient outcomes and highlights the prognostic value of genes. The developed prognostic nomogram, incorporating these genes along with clinical factors, provides a reliable tool for predicting patient survival probabilities and has important implications for personalized treatment decisions in glioma.

摘要

背景

神经胶质瘤是侵袭性脑肿瘤,预后较差。了解神经胶质瘤中的肿瘤免疫微环境(TIME)对于开发有效的免疫疗法至关重要。本研究旨在通过对RNA测序数据进行生物信息学分析,确定神经胶质瘤中与TIME相关的生物标志物。

方法

在本研究中,我们对批量RNA测序数据采用加权基因共表达网络分析(WGCNA)来识别与TIME相关的基因。为了识别预后基因,我们进行了单变量Cox回归和最小绝对收缩和选择算子(LASSO)回归分析。基于这些基因,我们构建了一个预后特征并划分了风险组。为了验证预后特征,我们进行了外部验证。

结果

CD8 + T细胞浸润与神经胶质瘤患者的预后密切相关。通过对批量测序数据的综合分析,我们确定了115个与CD8 + T细胞相关的基因。发现CDCA5、KIF11和KIF4A是与神经胶质瘤患者总生存期相关的重要免疫相关基因(IRGs),并作为独立的预后因素。我们开发了一个包含这些基因、年龄、性别和分级的预后列线图,为临床医生预测患者生存概率提供了一个可靠的工具。校准图支持列线图的预测,进一步验证了其准确性。

结论

总之,我们的研究确定CD8 + T细胞浸润是神经胶质瘤患者预后的有力预测指标,并突出了基因的预后价值。所开发的预后列线图结合了这些基因以及临床因素,为预测患者生存概率提供了一个可靠的工具,对神经胶质瘤的个性化治疗决策具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3408/11443942/417a24056722/12935_2024_3517_Fig1_HTML.jpg

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