Multi-Omics Analysis Reveals Novel Subtypes and Driver Genes in Glioblastoma.

Multi-Omics Analysis Reveals Novel Subtypes and Driver Genes in Glioblastoma.
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多组学分析揭示胶质母细胞瘤的新亚型和驱动基因

DOI:
10.3389/fgene.2020.565341
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发表时间:
2020
影响因子:
3.7
通讯作者:
Qing M
Qing M
中科院分区:
生物学3区
文献类型:
--
作者:
Yuan Y;Qi P;Xiang W;Yanhui L;Yu L;Qing M

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胶质母细胞瘤是最致命的恶性原发性脑肿瘤;然而,仍然缺乏准确的预后标志物和药物靶点。在这项研究中,我们分析了117例原发性胶质母细胞瘤患者的数据,包括SNP,DNA拷贝,DNA甲基化,mRNA表达和临床信息。质控检查后,进行单核苷酸多态性(SNP)分析、拷贝数变异(CNV)分析和免疫细胞浸润估计。此外,通过聚类分析(CoCA)方法,我们最终将这些GBM患者分为两个新的亚型,HX-1(第1组)和HX-2(簇2),其可以通过3个甲基化可变位置[cg 16957313(DUSP 1)、cg 17783509(PHOX 2B)、cg 23432345(HOXA 7)]和15个甲基化可变位置[cg 23432345(HOXA 7)]共同表征。(PCDH 1、CYP 27 B1、LPIN 3、GPR 32、BCL 6、OR 4 Q3、MAGI 3、SKIV 2L、PCSK 5、AKAP 12、UBE 3B、MAP 4、TP 53 BP 1、F5、RHOBTB 1)基因突变模式。与HX-1亚型相比,HX-2亚型的基因共现事件、肿瘤突变负荷(TBM)和中位总生存期较差[231.5天(HX-2)vs. 445天(HX-1),P值= 0.00053]。我们认为HX-1和HX-2亚型可能作为胶质母细胞瘤患者的潜在预后生物标志物。
Glioblastoma is the most lethal malignant primary brain tumor; nevertheless, there remains a lack of accurate prognostic markers and drug targets. In this study, we analyzed 117 primary glioblastoma patients’ data that contained SNP, DNA copy, DNA methylation, mRNA expression, and clinical information. After the quality of control examination, we conducted the single nucleotide polymorphism (SNP) analysis, copy number variation (CNV) analysis, and infiltrated immune cells estimate. And moreover, by using the cluster of cluster analysis (CoCA) methods, we finally divided these GBM patients into two novel subtypes, HX-1 (Cluster 1) and HX-2 (Cluster 2), which could be co-characterized by 3 methylation variable positions [cg16957313(DUSP1), cg17783509(PHOX2B), cg23432345(HOXA7)] and 15 (PCDH1, CYP27B1, LPIN3, GPR32, BCL6, OR4Q3, MAGI3, SKIV2L, PCSK5, AKAP12, UBE3B, MAP4, TP53BP1, F5, RHOBTB1) gene mutations pattern. Compared to HX-1 subtype, the HX-2 subtype was identified with higher gene co-occurring events, tumor mutation burden (TBM), and poor median overall survival [231.5 days (HX-2) vs. 445 days (HX-1), P-value = 0.00053]. We believe that HX-1 and HX-2 subtypes may make sense as the potential prognostic biomarkers for patients with glioblastoma.
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发表时间: 2015-04-20
影响因子: 14.9
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发表时间: 2019-08-31
期刊: AGING-US
影响因子: 5.2
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