基于放射基因组的全球DNA甲基化与胶质瘤分子表型及免疫特征的相关性分析

Radiogenomic profiling of global DNA methylation associated with molecular phenotypes and immune features in glioma

BMC Medicine

影响因子:8.3

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

DOI: 10.1186/s12916-024-03573-y

摘要

放射基因组分析为胶质瘤提供了具有生物学意义的宝贵影像生物标志物。用于分子特征如DNA甲基化的放射基因组标志物仍待揭示，以辅助分子诊断和肿瘤治疗。我们应用机器学习方法，识别146例胶质瘤患者的磁共振成像（MRI）特征，这些特征与分子表型相关，并为每个分子特征（MoRad）开发并验证了拟合模型。为提供分子表型的放射学注释，我们提出了两种新颖的方法：放射肿瘤学（RO）和放射组富集分析（RSEA）。所生成的MoRad模型在利用放射组学特征对各类分子特征（包括突变、甲基化、转录以及蛋白质谱）进行表型分析方面表现良好。其中，MoRad模型在定量映射全球DNA甲基化方面表现尤为出色。通过RO和RSEA方法，我们发现全球DNA甲基化可通过T2加权MRI增强区域的体积和纹理异质性反映出来。最后，我们展示了全球DNA甲基化与临床病理学、分子和免疫特征的关联，包括组织学等级、IDH和ATRX突变、MGMT甲基化、多重高甲基化亚型、肿瘤浸润淋巴细胞及长期存活结果。全球DNA甲基化与胶质瘤的放射学特征高度相关。放射基因组学的全球甲基化是一种基于影像的定量分子生物标志物，关联特定的共识分子亚型和免疫特征。

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.