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肿瘤位置、基因组改变和放射组学特征作为胶质母细胞瘤生存的预测指标:一项多模态分析

Tumor location, genomic alterations, and radiomic features as predictors of survival in glioblastoma: a Multi-Modal analysis.

作者信息

Kundal Kavita, Rao K Venkateswara, Dhanda Sandeep Kumar, Kumar Neeraj, Kumar Rahul

机构信息

Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, India.

Basavatarakam Indo American Cancer Hospital & Research Institute, Hyderabad, India.

出版信息

Neuroradiology. 2025 Aug 12. doi: 10.1007/s00234-025-03742-7.

Abstract

PURPOSE

This study aims to identify the impact of tumor location on the survival of glioblastoma (GBM) patients and the associated genetic alterations, using MRI scans from The Cancer Imaging Archive (TCIA) and genomic data from The Cancer Genome Atlas (TCGA). It also seeks to uncover non-invasive radiomic markers related to poor survival outcome for improved prognosis and treatment planning.

METHODS

We analysed pre-operative MRI scans and genomic data from 123 GBM patients (TCIA and TCGA). Tumor locations were determined using our in-house tool, "tumorVQ", followed by Kaplan-Meier survival analysis based on tumor position. Genomic analysis included somatic mutations, copy number variations, fusion genes, and differential gene expression to identify factors linked to poor survival. We extracted radiomic features from T1ce MRI scans using pyRadiomics to analyse their relationship with survival outcomes.

RESULTS

Kaplan-Meier analysis showed worse survival for tumors in the parietal lobe compared to other lobes, especially frontal lobe tumors. Genomic analysis revealed high prevalence of PTEN mutations, and exclusive fusion genes FGFR3-TACC3 and EGFR-SEPT14 in parietal lobe tumors. Differential gene expression showed upregulation of PITX2, HOXB13, and DTHD1, linked to tumor progression, while ALOX15 downregulation increased relapse risk. Copy number alterations, like LINC00290 deletions, were associated with aggressive parietal lobe tumors. Radiomic features, lower GLDM DependanceEntropy (LLL) and higher FirstOrder Mean (HLL), were strongly linked to increase risk.

CONCLUSION

This study highlights poor survival outcomes in GBM patients with parietal lobe tumors. Key genetic alterations, such as PTEN mutations and fusion genes, drive tumor progression and chemoresistance in parietal lobe tumors. The association between radiomic features and survival indicates their potential as non-invasive prognostic biomarkers, which could aid in personalized treatment and improved patient management.

摘要

目的

本研究旨在利用来自癌症影像存档库(TCIA)的MRI扫描数据和来自癌症基因组图谱(TCGA)的基因组数据,确定肿瘤位置对胶质母细胞瘤(GBM)患者生存情况及相关基因改变的影响。同时,本研究还试图发现与不良生存结局相关的非侵入性放射组学标志物,以改善预后和治疗规划。

方法

我们分析了123例GBM患者(TCIA和TCGA)的术前MRI扫描数据和基因组数据。使用我们内部的工具“tumorVQ”确定肿瘤位置,随后基于肿瘤位置进行Kaplan-Meier生存分析。基因组分析包括体细胞突变、拷贝数变异、融合基因和差异基因表达,以确定与不良生存相关的因素。我们使用pyRadiomics从T1ce MRI扫描中提取放射组学特征,以分析它们与生存结局的关系。

结果

Kaplan-Meier分析显示,与其他脑叶的肿瘤相比,顶叶肿瘤患者的生存情况更差,尤其是额叶肿瘤患者。基因组分析显示,PTEN突变在顶叶肿瘤中普遍存在,且顶叶肿瘤中存在独特的融合基因FGFR3-TACC3和EGFR-SEPT14。差异基因表达显示,与肿瘤进展相关的PITX2、HOXB13和DTHD1上调,而ALOX15下调增加了复发风险。拷贝数改变,如LINC00290缺失,与侵袭性顶叶肿瘤相关。放射组学特征,如较低的GLDM依赖熵(LLL)和较高的一阶均值(HLL),与风险增加密切相关。

结论

本研究突出了顶叶肿瘤GBM患者不良的生存结局。关键的基因改变,如PTEN突变和融合基因,驱动顶叶肿瘤的进展和化疗耐药性。放射组学特征与生存之间的关联表明它们作为非侵入性预后生物标志物的潜力,这有助于个性化治疗和改善患者管理。

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