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基于计算机断层扫描的放射组学可预测透明细胞肾细胞癌免疫微环境中免疫浸润的预后及治疗相关水平。

Computed tomography-based radiomics predicts prognostic and treatment-related levels of immune infiltration in the immune microenvironment of clear cell renal cell carcinoma.

作者信息

Song Shiyan, Ge Wenfei, Qi Xiaochen, Che Xiangyu, Wang Qifei, Wu Guangzhen

机构信息

Department of Urology, The First Affiliated Hospital of Dalian Medical University, No.222 Zhongshan Road, Dalian, Liaoning, 116011, PR China.

出版信息

BMC Med Imaging. 2025 Jul 1;25(1):213. doi: 10.1186/s12880-025-01749-3.

DOI:10.1186/s12880-025-01749-3
PMID:40596969
Abstract

OBJECTIVES

The composition of the tumour microenvironment is very complex, and measuring the extent of immune cell infiltration can provide an important guide to clinically significant treatments for cancer, such as immune checkpoint inhibition therapy and targeted therapy. We used multiple machine learning (ML) models to predict differences in immune infiltration in clear cell renal cell carcinoma (ccRCC), with computed tomography (CT) imaging pictures serving as a model for machine learning. We also statistically analysed and compared the results of multiple typing models and explored an excellent non-invasive and convenient method for treatment of ccRCC patients and explored a better, non-invasive and convenient prediction method for ccRCC patients.

METHODS

The study included 539 ccRCC samples with clinicopathological information and associated genetic information from The Cancer Genome Atlas (TCGA) database. The Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to obtain the immune cell infiltration results as well as the cluster analysis results. ssGSEA-based analysis was used to obtain the immune cell infiltration levels, and the Boruta algorithm was further used to downscale the obtained positive/negative gene sets to obtain the immune infiltration level groupings. Multifactor Cox regression analysis was used to calculate the immunotherapy response of subgroups according to Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and subgraph algorithm to detect the difference in survival time and immunotherapy response of ccRCC patients with immune infiltration. Radiomics features were screened using LASSO analysis. Eight ML algorithms were selected for diagnostic analysis of the test set. Receiver operating characteristic (ROC) curve was used to evaluate the performance of the model. Draw decision curve analysis (DCA) to evaluate the clinical personalized medical value of the predictive model.

RESULTS

The high/low subtypes of immune infiltration levels obtained by optimisation based on the Boruta algorithm were statistically different in the survival analysis of ccRCC patients. Multifactorial immune infiltration level combined with clinical factors better predicted survival of ccRCC patients, and ccRCC with high immune infiltration may benefit more from anti-PD-1 therapy. Among the eight machine learning models, ExtraTrees had the highest test and training set ROC AUCs of 1.000 and 0.753; in the test set, LR and LightGBM had the highest sensitivity of 0.615; LR, SVM, ExtraTrees, LightGBM and MLP had higher specificities of 0.789, 1.000, 0.842, 0.789 and 0.789, respectively; and LR, ExtraTrees and LightGBM had the highest accuracy of 0. 719, 0.688 and 0.719 respectively. Therefore, the CT-based ML achieved good predictive results in predicting immune infiltration in ccRCC, with the ExtraTrees machine learning algorithm being optimal.

CONCLUSION

The use of radiomics model based on renal CT images can be noninvasively used to predict the immune infiltration level of ccRCC as well as combined with clinical information to create columnar plots predicting total survival in people with ccRCC and to predict responsiveness to ICI therapy, findings that may be useful in stratifying the prognosis of patients with ccRCC and guiding clinical practitioners to develop individualized regimens in the treatment of their patients.

摘要

目的

肿瘤微环境的组成非常复杂,测量免疫细胞浸润程度可为癌症的临床重要治疗提供重要指导,如免疫检查点抑制疗法和靶向治疗。我们使用多种机器学习(ML)模型来预测透明细胞肾细胞癌(ccRCC)中免疫浸润的差异,将计算机断层扫描(CT)影像图片作为机器学习的模型。我们还对多种分型模型的结果进行了统计分析和比较,探索一种用于ccRCC患者治疗的优秀的非侵入性且便捷的方法,并为ccRCC患者探索一种更好的、非侵入性且便捷的预测方法。

方法

该研究纳入了来自癌症基因组图谱(TCGA)数据库的539个具有临床病理信息和相关基因信息的ccRCC样本。使用单样本基因集富集分析(ssGSEA)算法获得免疫细胞浸润结果以及聚类分析结果。基于ssGSEA的分析用于获得免疫细胞浸润水平,进一步使用博鲁塔(Boruta)算法对获得的阳性/阴性基因集进行降维,以获得免疫浸润水平分组。使用多因素Cox回归分析根据肿瘤免疫功能障碍和排除(TIDE)算法计算亚组的免疫治疗反应,并使用子图算法检测免疫浸润的ccRCC患者的生存时间和免疫治疗反应差异。使用LASSO分析筛选影像组学特征。选择八种ML算法对测试集进行诊断分析。使用受试者工作特征(ROC)曲线评估模型性能。绘制决策曲线分析(DCA)以评估预测模型的临床个性化医疗价值。

结果

基于博鲁塔算法优化得到的免疫浸润水平高/低亚型在ccRCC患者的生存分析中具有统计学差异。多因素免疫浸润水平结合临床因素能更好地预测ccRCC患者的生存情况,且免疫浸润高的ccRCC可能从抗PD - 1治疗中获益更多。在八种机器学习模型中,ExtraTrees在测试集和训练集的ROC AUC最高,分别为1.000和0.753;在测试集中,LR和LightGBM的灵敏度最高,为0.615;LR、SVM、ExtraTrees、LightGBM和MLP的特异性较高,分别为0.789、1.000、0.842、0.789和0.789;LR、ExtraTrees和LightGBM的准确率最高,分别为0.719、0.688和0.719。因此,基于CT的ML在预测ccRCC免疫浸润方面取得了良好的预测结果,其中ExtraTrees机器学习算法最优。

结论

基于肾脏CT图像的影像组学模型可用于无创预测ccRCC的免疫浸润水平,并结合临床信息创建预测ccRCC患者总生存的柱状图以及预测对ICI治疗的反应,这些发现可能有助于对ccRCC患者的预后进行分层,并指导临床医生为其患者制定个体化治疗方案。

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Radiomics predicts the prognosis of patients with clear cell renal cell carcinoma by reflecting the tumor heterogeneity and microenvironment.放射组学通过反映肿瘤异质性和微环境来预测透明细胞肾细胞癌患者的预后。
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