与分子表型相关的全球DNA甲基化的放射基因组学分析和神经胶质瘤中的免疫特征
Radiogenomic profiling of global DNA methylation associated with molecular phenotypes and immune features in glioma
影响因子:8.30000
分区:医学1区 Top / 医学：内科1区
发表日期:2024 Sep 02
作者:
Zhuokai Zhuang, Jinxin Lin, Zixiao Wan, Jingrong Weng, Ze Yuan, Yumo Xie, Zongchao Liu, Peiyi Xie, Siyue Mao, Zongming Wang, Xiaolin Wang, Meijin Huang, Yanxin Luo, Huichuan Yu
摘要
放射基因组分析为胶质瘤提供了有价值的成像生物标志物。分子概况（例如DNA甲基化）的放射基因标记物仍有待发现以帮助分子诊断和肿瘤治疗。我们采用机器学习方法来识别与146名具有Gliomas患者的分子谱相关的磁共振成像（MRI）特征，并具有分子型模型，以及每种分子特征的拟合模型（MORAD）（MORAD和MORAD）。为了提供分子特征的放射学注释，我们设计了两种称为放射线肿瘤学（RO）和放射线集合富集分析（RSEA）的新型方法。生成的MORAD模型在每个分子特征均具有放射性特征，包括突变，甲基化，转录，转录和蛋白质概要液。其中，Morad模型在定量映射全局DNA甲基化方面具有出色的性能。使用RO和RSEA方法，我们发现全球DNA甲基化可以通过T2加权MRI增强区域的体积和质地特征的异质性反映。最后，我们证明了全球DNA甲基化与临床病理学，分子和免疫学特征的关联，包括组织学等级，IDH和ATRX的突变，MGMT甲基化，多重甲基化亚型，肿瘤浸入肿瘤浸润的淋巴细胞，以及长期的淋巴细胞，以及长期的生存率均与GLI群体相关。放射基因组全球甲基化是一种基于成像的定量分子生物标志物，与特定共有的分子亚型和免疫特征有关。
Abstract
The radiogenomic analysis has provided valuable imaging biomarkers with biological insights for gliomas. The radiogenomic markers for molecular profile such as DNA methylation remain to be uncovered to assist the molecular diagnosis and tumor treatment.We apply the machine learning approaches to identify the magnetic resonance imaging (MRI) features that are associated with molecular profiles in 146 patients with gliomas, and the fitting models for each molecular feature (MoRad) are developed and validated. To provide radiological annotations for the molecular profiles, we devise two novel approaches called radiomic oncology (RO) and radiomic set enrichment analysis (RSEA).The generated MoRad models perform well for profiling each molecular feature with radiomic features, including mutational, methylation, transcriptional, and protein profiles. Among them, the MoRad models have a remarkable performance in quantitatively mapping global DNA methylation. With RO and RSEA approaches, we find that global DNA methylation could be reflected by the heterogeneity in volumetric and textural features of enhanced regions in T2-weighted MRI. Finally, we demonstrate the associations of global DNA methylation with clinicopathological, molecular, and immunological features, including histological grade, mutations of IDH and ATRX, MGMT methylation, multiple methylation-high subtypes, tumor-infiltrating lymphocytes, and long-term survival outcomes.Global DNA methylation is highly associated with radiological profiles in glioma. Radiogenomic global methylation is an imaging-based quantitative molecular biomarker that is associated with specific consensus molecular subtypes and immune features.