Department of Urology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Radiology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Cancer Med. 2023 Mar;12(6):7627-7638. doi: 10.1002/cam4.5449. Epub 2022 Nov 17.
To predict CTLA4 expression levels and prognosis of clear cell renal cell carcinoma (ccRCC) by constructing a computed tomography-based radiomics model and establishing a nomogram using clinicopathologic factors.
The clinicopathologic parameters and genomic data were extracted from 493 ccRCC cases of the Cancer Genome Atlas (TCGA)-KIRC database. Univariate and multivariate Cox regression and Kaplan-Meier analysis were performed for prognosis analysis. Cibersortx was applied to evaluate the immune cell composition. Radiomic features were extracted from the TCGA/the Cancer Imaging Archive (TCIA) (n = 102) datasets. The support vector machine (SVM) was employed to establish the radiomics signature for predicting CTLA4 expression. Receiver operating characteristic curve (ROC), decision curve analysis (DCA), and precision-recall curve were utilized to assess the predictive performance of the radiomics signature. Correlations between radiomics score (RS) and selected features were also evaluated. An RS-based nomogram was constructed to predict prognosis.
CTLA4 was significantly overexpressed in ccRCC tissues and was related to lower overall survival. A higher CTLA4 expression was independently linked to the poor prognosis (HR = 1.458, 95% CI 1.13-1.881, p = 0.004). The radiomics model for the prediction of CTLA4 expression levels (AUC = 0.769 in the training set, AUC = 0.724 in the validation set) was established using seven radiomic features. A significant elevation in infiltrating M2 macrophages was observed in the RS high group (p < 0.001). The predictive efficiencies of the RS-based nomogram measured by AUC were 0.826 at 12 months, 0.805 at 36 months, and 0.76 at 60 months.
CTLA4 mRNA expression status in ccRCC could be predicted noninvasively using a radiomics model based on nephrographic phase contrast-enhanced CT images. The nomogram established by combining RS and clinicopathologic factors could predict overall survival for ccRCC patients. Our findings may help stratify prognosis of ccRCC patients and identify those who may respond best to ICI-based treatments.
通过构建基于 CT 的放射组学模型和利用临床病理因素建立列线图,预测透明细胞肾细胞癌(ccRCC)的 CTLA4 表达水平和预后。
从癌症基因组图谱(TCGA)-KIRC 数据库的 493 例 ccRCC 病例中提取临床病理参数和基因组数据。进行单因素和多因素 Cox 回归及 Kaplan-Meier 分析进行预后分析。应用 Cibersortx 评估免疫细胞组成。从 TCGA/癌症成像档案(TCIA)(n=102)数据集提取放射组学特征。采用支持向量机(SVM)建立预测 CTLA4 表达的放射组学特征。使用受试者工作特征曲线(ROC)、决策曲线分析(DCA)和精度-召回曲线评估放射组学特征的预测性能。还评估了放射组学评分(RS)与选定特征之间的相关性。构建基于 RS 的列线图以预测预后。
CTLA4 在 ccRCC 组织中过表达,与总生存期降低相关。较高的 CTLA4 表达与不良预后独立相关(HR=1.458,95%CI 1.13-1.881,p=0.004)。用于预测 CTLA4 表达水平的放射组学模型(在训练集中 AUC=0.769,在验证集中 AUC=0.724)是使用 7 个放射组学特征建立的。在 RS 高组中观察到浸润性 M2 巨噬细胞显著增加(p<0.001)。基于 RS 的列线图的预测效率通过 AUC 在 12 个月时为 0.826,在 36 个月时为 0.805,在 60 个月时为 0.76。
可以使用基于肾实质期对比增强 CT 图像的放射组学模型无创预测 ccRCC 中的 CTLA4 mRNA 表达状态。通过结合 RS 和临床病理因素建立的列线图可预测 ccRCC 患者的总生存期。我们的研究结果可能有助于对 ccRCC 患者进行分层,以确定最有可能对 ICI 治疗有反应的患者。