基于肿瘤免疫微环境鉴定IDH突变型弥漫性胶质瘤的预后标志物

Prognostic markers of IDH mutant diffuse glioma based on tumor immune microenvironment

异柠檬酸脱氢酶(IDH)突变存在于大多数低级别胶质细胞瘤中,免疫逃逸是肿瘤标志性特征之一,免疫治疗在胶质瘤的治疗中的作用越来越重要。利用生信手段分析TCGA、CGGA、GEO数据集中IDH突变胶质瘤的770个免疫相关基因及其临床相关数据,从而获得每个患者的免疫风险评分(IMRS);结合IMRS和临床信息,筛选出6个差异表达基因(TRAF3、ATG10、BID、TAB1、MAP3K1、RPS6)组成IMRS模型并生成诺莫图对患者预后进行评估,发现低风险组患者的总生存期(OS)较高风险组均明显延长。此外,签名相关免疫细胞浸润分析发现肿瘤相关巨噬细胞浸润评分(TAM)与肿瘤相关T细胞浸润评分(TIS)呈明显的负相关,表明高IMRS富集了促肿瘤免疫浸润,而低IMRS则富集了相对较多的抗肿瘤免疫浸润。

IDH mutations are present in most low-grade gliomas. Immue escape is one of the landmarks of tumor, and immunotherapy is a new direction of tumor therapy. A total of 770 immune-related genes and clinical data of IDH mutant glioma in TCGA, CGGA, and GEO datasets were analyzed by bioinformatics method, so as to obtain the immune risk score(IMRS) for each patient. Combined with IMRS and clinical information, six differentially expressed genes(TRAF3,ATG10,BID,TAB1,MAP3K1,RPS6) were screened to form IMRS model and nomograms were generated to evaluate the prognosis of patients.It was found that the overall survival(OS) of patients in low risk group was obviously in creased compared with that in high risk group. In addition, the signature related immune cell infiltration analysis showed that tumor associated macrophages infiltration score(TAM) and T cell associated tumor infiltrating score(TIS) were significantly negatively correlated, indicating that high IMRS enriches pro-tumor immune infiltration, while low IMRS enriches relatively more anti-tumor immune infiltration.