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全面定量放射基因组学评估揭示了胶质瘤中具有不同免疫模式的新型放射组学分型。

Comprehensive quantitative radiogenomic evaluation reveals novel radiomic subtypes with distinct immune pattern in glioma.

机构信息

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

出版信息

Comput Biol Med. 2024 Jul;177:108636. doi: 10.1016/j.compbiomed.2024.108636. Epub 2024 May 20.

Abstract

BACKGROUND

Accurate classification of gliomas is critical to the selection of immunotherapy, and MRI contains a large number of radiomic features that may suggest some prognostic relevant signals. We aim to predict new subtypes of gliomas using radiomic features and characterize their survival, immune, genomic profiles and drug response.

METHODS

We initially obtained 341 images of 36 patients from the CPTAC dataset for the development of deep learning models. Further 1812 images of 111 patients from TCGA_GBM and 152 images of 53 patients from TCGA_LGG were collected for testing and validation. A deep learning method based on Mask R-CNN was developed to identify new subtypes of glioma patients and compared the survival status, immune infiltration patterns, genomic signatures, specific drugs, and predictive models of different subtypes.

RESULTS

200 glioma patients (mean age, 33 years ± 19 [standard deviation]) were enrolled. The accuracy of the deep learning model for identifying tumor regions achieved 88.3 % (98/111) in the test set and 83 % (44/53) in the validation set. The sample was divided into two subtypes based on radiomic features showed different prognostic outcomes (hazard ratio, 2.70). According to the results of the immune infiltration analysis, the subtype with a poorer prognosis was defined as the immunosilencing radiomic (ISR) subtype (n = 43), and the other subtype was the immunoactivated radiomic (IAR) subtype (n = 53). Subtype-specific genomic signatures distinguished celllines into ISR celllines (n = 9) and control celllines (n = 13), and identified eight ISR-specific drugs, four of which were validated by the OCTAD database. Three machine learning-based classifiers showed that radiomic and genomic co-features better predicted the radiomic subtypes of gliomas.

CONCLUSIONS

These findings provide insights into how radiogenomic could identify specific subtypes that predict prognosis, immune and drug sensitivity in a non-invasive manner.

摘要

背景

准确的胶质瘤分类对于免疫治疗的选择至关重要,而 MRI 包含大量的放射组学特征,这些特征可能提示一些与预后相关的信号。我们旨在使用放射组学特征预测新的胶质瘤亚型,并描述其生存、免疫、基因组特征和药物反应。

方法

我们最初从 CPTAC 数据集获得了 36 名患者的 341 张图像,用于开发深度学习模型。进一步从 TCGA_GBM 中收集了 111 名患者的 1812 张图像和 TCGA_LGG 中的 53 名患者的 152 张图像用于测试和验证。开发了一种基于 Mask R-CNN 的深度学习方法来识别新的胶质瘤患者亚型,并比较不同亚型的生存状态、免疫浸润模式、基因组特征、特定药物和预测模型。

结果

共纳入 200 名胶质瘤患者(平均年龄 33 岁±19 岁[标准差])。深度学习模型对肿瘤区域的识别准确率在测试集和验证集分别达到 88.3%(98/111)和 83%(44/53)。根据放射组学特征将样本分为两种亚型,表现出不同的预后结果(风险比,2.70)。根据免疫浸润分析结果,预后较差的亚型被定义为免疫抑制放射组学(ISR)亚型(n=43),另一个亚型被定义为免疫激活放射组学(IAR)亚型(n=53)。亚型特异性基因组特征将细胞系分为 ISR 细胞系(n=9)和对照细胞系(n=13),并鉴定出八种 ISR 特异性药物,其中四种药物在 OCTAD 数据库中得到验证。三种基于机器学习的分类器表明,放射组学和基因组特征协同可以更好地预测胶质瘤的放射组学亚型。

结论

这些发现为放射基因组学如何以非侵入性方式识别预测预后、免疫和药物敏感性的特定亚型提供了思路。

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