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基于ERK/MAPK通路的IDH野生型胶质母细胞瘤多平台分类:诊断、预后及治疗意义

Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic Implications.

作者信息

Georgescu Maria-Magdalena

机构信息

NeuroMarkers PLLC, Houston, TX 77025, USA.

出版信息

Cancers (Basel). 2021 Sep 9;13(18):4532. doi: 10.3390/cancers13184532.

Abstract

Glioblastoma is the most aggressive and frequent glioma in the adult population. Because current therapy regimens confer only minimal survival benefit, molecular subgrouping to stratify patient prognosis and therapy design is warranted. This study presents a multi-platform classification of glioblastoma by analyzing a large, ethnicity-inclusive 101-adult-patient cohort. It defines seven non-redundant IDH-wild-type glioblastoma molecular subgroups, G1-G7, corresponding to the upstream receptor tyrosine kinase (RTK) and RAS-RAF segment of the ERK/MAPK signal transduction pathway. These glioblastoma molecular subgroups are classified as G1/EGFR, G2/FGFR3, G3/NF1, G4/RAF, G5/PDGFRA, G6/Multi-RTK, and G7/Other. The comprehensive genomic analysis was refined by expression landscaping of all RTK genes, as well as of the major associated growth pathway mediators, and used to hierarchically cluster the subgroups. Parallel demographic, clinical, and histologic pattern analyses were merged with the molecular subgrouping to yield the first inclusive multi-platform classification for IDH-wild-type glioblastoma. This straightforward classification with diagnostic and prognostic significance may be readily used in neuro-oncological practice and lays the foundation for personalized targeted therapy approaches.

摘要

胶质母细胞瘤是成人中最具侵袭性且最常见的胶质瘤。由于目前的治疗方案仅能带来极小的生存获益,因此有必要进行分子亚组分类以分层患者预后并设计治疗方案。本研究通过分析一个包含101名成年患者、涵盖不同种族的大型队列,对胶质母细胞瘤进行了多平台分类。研究定义了七个非冗余的异柠檬酸脱氢酶(IDH)野生型胶质母细胞瘤分子亚组,即G1 - G7,它们对应于细胞外信号调节激酶/丝裂原活化蛋白激酶(ERK/MAPK)信号转导通路的上游受体酪氨酸激酶(RTK)和RAS - RAF部分。这些胶质母细胞瘤分子亚组被分类为G1/表皮生长因子受体(EGFR)、G2/成纤维细胞生长因子受体3(FGFR3)、G3/神经纤维瘤病1型(NF1)、G4/RAF、G5/血小板衍生生长因子受体α(PDGFRA)、G6/多种RTK和G7/其他。通过对所有RTK基因以及主要相关生长通路介质进行表达景观分析,对全面的基因组分析进行了优化,并用于对亚组进行层次聚类。将平行的人口统计学、临床和组织学模式分析与分子亚组分类相结合,得出了首个针对IDH野生型胶质母细胞瘤的包容性多平台分类。这种具有诊断和预后意义的直接分类可在神经肿瘤学实践中轻松应用,并为个性化靶向治疗方法奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7e8/8470497/cbe71f7e7230/cancers-13-04532-g001.jpg

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