Deng Xiangyang, Chen Kezhu, Ren Junwei, Zeng Jun, Zhang Quan, Li Tianwen, Tang Qisheng, Zhu Jianhong
Fudan University Huashan Hospital, Department of Neurosurgery, National Center for Neurological Disorders, National Key Laboratory for Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College-Fudan University, Shanghai, China.
Front Mol Biosci. 2022 Jul 19;9:849723. doi: 10.3389/fmolb.2022.849723. eCollection 2022.
The B7-CD28 gene family plays a crucial role in modulating immune functions and has served as potential targets for immunotherapeutic strategies. Therefore, we systematically analyzed B7-CD28 family gene expression profiles and constructed a B7-CD28 family-based prognostic signature to predict survival and immune host status in diffuse gliomas. The TCGA dataset was used as a training cohort, and three CGGA datasets (mRNAseq_325, mRNAseq_693 and mRNA-array) were employed as validation cohorts to intensify the findings that we have revealed in TCGA dataset. Ultimately, we developed a B7-CD28 family-based signature that consisted of CD276, CD274, PDCD1LG2 and CD80 using LASSO Cox analysis. This gene signature was validated to have significant prognostic value, and could be used as a biomarker to distinguish pathological grade and IDH mutation status in diffuse glioma. Additionally, we found that the gene signature was significantly related to intensity of immune response and immune cell population, as well as several other important immune checkpoint genes, holding a great potential to be a predictive immune marker for immunotherapy and tumor microenvironment. Finally, a B7-CD28 family-based nomogram was established to predict patient life expectancy contributing to facilitate personalizing therapy for tumor sufferers. In summary, this is the first mathematical model based on this gene family with the aim of providing novel insights into immunotherapy for diffuse glioma.
B7 - CD28基因家族在调节免疫功能中起关键作用，并已成为免疫治疗策略的潜在靶点。因此，我们系统地分析了B7 - CD28家族基因表达谱，并构建了基于B7 - CD28家族的预后特征，以预测弥漫性胶质瘤患者的生存情况和免疫宿主状态。使用TCGA数据集作为训练队列，并采用三个CGGA数据集（mRNAseq_325、mRNAseq_693和mRNA - array）作为验证队列，以强化我们在TCGA数据集中所揭示的发现。最终，我们使用LASSO Cox分析开发了一个基于B7 - CD28家族的特征，该特征由CD276、CD274、PDCD1LG2和CD80组成。该基因特征被验证具有显著的预后价值，可作为区分弥漫性胶质瘤病理分级和异柠檬酸脱氢酶（IDH）突变状态的生物标志物。此外，我们发现该基因特征与免疫反应强度、免疫细胞群体以及其他几个重要的免疫检查点基因显著相关，具有成为免疫治疗和肿瘤微环境预测性免疫标志物的巨大潜力。最后，建立了一个基于B7 - CD28家族的列线图来预测患者预期寿命，有助于为肿瘤患者制定个性化治疗方案。总之，这是第一个基于该基因家族的数学模型，旨在为弥漫性胶质瘤的免疫治疗提供新的见解。
