Zhou Jie
Shenzhen Hospital (Longgang), Beijing University of Chinese Medicine, Shenzhen, China.
J Transl Med. 2025 Mar 31;23(1):383. doi: 10.1186/s12967-025-06402-9.
High-grade gliomas are among the most aggressive and deadly brain tumors, highlighting the critical need for improved prognostic markers and predictive models. Recent studies have identified the expression of IL7R as a significant risk factor that affects the prognosis of patients diagnosed with high-grade gliomas (HGG). This research focuses on investigating the prognostic significance of Interleukin 7 Receptor (IL7R) expression and aims to develop a noninvasive predictive model based on radiomics for HGG.
We conducted an analysis using data from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA), focusing on a group of 310 patients diagnosed with high-grade gliomas. To evaluate prognosis, we applied both univariate and multivariate Cox regression analyses alongside Kaplan-Meier survival analysis. Radiomics features were extracted from specific regions of interest, which were outlined by two physicians using 3D Slicer software. For selecting the most relevant features, we utilized the Minimum Redundancy Maximum Relevance (mRMR) and Recursive Feature Elimination (RFE) algorithms. Following this, we developed and assessed Support Vector Machine (SVM) and Logistic Regression (LR) models, measuring their performance through various metrics such as accuracy, specificity, sensitivity, positive predictive value, calibration curves, the Hosmer-Lemeshow goodness-of-fit test, decision curve analysis (DCA), and Kaplan-Meier survival analysis.
The survival analysis encompassed a total of 310 patients diagnosed with high-grade glioma, sourced from the TCGA database. Patients were stratified into high and low expression groups based on the levels of IL7R expression. Kaplan-Meier survival curves and Cox regression analysis revealed that an increase in IL7R expression correlated with a decline in overall survival (OS). The median Intraclass Correlation Coefficient (ICC) for the assessed radiomic features was determined to be 0.869, with 93 features exhibiting an ICC of 0.75 or greater. Utilizing the mRMR and RFE methodologies led to the identification of a final set comprising eight features. The Support Vector Machine (SVM) model recorded an Area Under the Curve (AUC) value of 0.805, whereas the AUC derived from fivefold cross-validation was noted to be 0.768. Conversely, the Logistic Regression (LR) model produced an AUC of 0.85, with an internal fivefold cross-validation AUC of 0.779, indicating a more robust predictive capability. We developed Support Vector Machine (SVM) and Logistic Regression (LR) models, with the LR model demonstrating a more robust predictive capability. Further Kaplan-Meier analysis underscored a significant association between elevated risk scores from the LR model and OS malignancy, with a P value of less than 0.001. GSVA analysis showed the enrichment pathway of KEGG and Hallmark genes in the high RS group. Moreover, expression levels of the LOX gene and the infiltration of M0 macrophages were significantly heightened in the high-risk score group, alongside an increase in tumor mutation burden (TMB). Interestingly, the mutation frequencies of TP53 and PIK3CA were found to be lower in the high-risk score group when compared to their low-risk counterparts.
IL7R expression is a vital prognostic marker in high-grade gliomas. The radiomics-based LR models demonstrate strong predictive capabilities for patient outcomes. Future investigations should aim to incorporate these insights into clinical practice to enhance personalized treatment approaches for patients with high-grade glioma.
高级别胶质瘤是最具侵袭性和致命性的脑肿瘤之一,凸显了对改进预后标志物和预测模型的迫切需求。最近的研究已确定白细胞介素7受体(IL7R)的表达是影响高级别胶质瘤(HGG)患者预后的一个重要风险因素。本研究聚焦于探讨白细胞介素7受体(IL7R)表达的预后意义,并旨在开发一种基于放射组学的HGG无创预测模型。
我们使用来自癌症基因组图谱(TCGA)和癌症影像存档(TCIA)的数据进行分析,研究对象为310例被诊断为高级别胶质瘤的患者。为评估预后,我们应用了单变量和多变量Cox回归分析以及Kaplan-Meier生存分析。从特定感兴趣区域提取放射组学特征,这些区域由两名医生使用3D Slicer软件勾勒。为选择最相关的特征,我们采用了最小冗余最大相关(mRMR)和递归特征消除(RFE)算法。在此之后,我们开发并评估了支持向量机(SVM)和逻辑回归(LR)模型,通过各种指标衡量其性能,如准确性、特异性、敏感性、阳性预测值、校准曲线、Hosmer-Lemeshow拟合优度检验、决策曲线分析(DCA)以及Kaplan-Meier生存分析。
生存分析涵盖了总共310例诊断为高级别胶质瘤的患者,数据来源于TCGA数据库。根据IL7R表达水平将患者分为高表达组和低表达组。Kaplan-Meier生存曲线和Cox回归分析显示,IL7R表达增加与总生存期(OS)下降相关。评估的放射组学特征的类内相关系数(ICC)中位数为0.869,93个特征的ICC为0.75或更高。利用mRMR和RFE方法最终确定了包含8个特征的集合。支持向量机(SVM)模型的曲线下面积(AUC)值为0.805,而五重交叉验证得出的AUC为0.768。相反,逻辑回归(LR)模型的AUC为0.85,内部五重交叉验证的AUC为0.779,表明其预测能力更强。我们开发了支持向量机(SVM)和逻辑回归(LR)模型,LR模型显示出更强的预测能力。进一步的Kaplan-Meier分析强调,LR模型的高风险评分与OS恶性程度之间存在显著关联,P值小于0.001。基因集变异分析(GSVA)显示高风险评分(RS)组中KEGG和标志性基因的富集途径。此外,高风险评分组中LOX基因的表达水平和M0巨噬细胞的浸润显著升高,同时肿瘤突变负担(TMB)增加。有趣的是,与低风险组相比,高风险评分组中TP53和PIK3CA的突变频率较低。
IL7R表达是高级别胶质瘤的重要预后标志物。基于放射组学的LR模型对患者预后具有强大的预测能力。未来的研究应旨在将这些见解纳入临床实践,以加强对高级别胶质瘤患者的个性化治疗方法。