Radiogenomic mapping of edema/cellular invasion MRI-phenotypes in glioblastoma multiforme.
Radiogenomic mapping of edema/cellular invasion MRI-phenotypes in glioblastoma multiforme.
复制标题
DOI：
10.1371/journal.pone.0025451
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Colen RR
中科院分区：
文献类型：
--
作者：
Zinn PO;Mahajan B;Sathyan P;Singh SK;Majumder S;Jolesz FA;Colen RR
尽管最近发现了新的分子靶点和途径，但对多形性胶质母细胞瘤（GBM）的有效治疗的研究仍在继续。一个新兴的领域，放射基因组学，链接基因表达谱与MRI表型。MRI-FLAIR是一种非侵入性诊断方法，以前发现与GBM中的细胞浸润相关。因此，我们的放射基因组筛选有可能揭示新的分子入侵的决定因素。在这里，我们提出了第一个全面的放射基因组学分析，使用定量MRI体积和大规模的基因和微小RNA表达谱GBM。基于癌症基因组图谱（TCGA），创建了包含基因、microRNA和定量MR成像数据的发现和验证集。通过Kaplan Meier生存统计学、microRNA-基因相关性分析和GBM分子亚型特异性分布进一步表征了两组中与高FLAIR体积相关的前一致基因和microRNA。在发现组（4倍）和验证组（11倍）中最高上调的基因是PERIOSTIN（POSTIN）。两组中下调最多的microRNA是miR-219，预测其与POL 4结合。Kaplan-Meier分析显示，POST 3表达高于中位值导致生存率显著降低和疾病进展时间缩短（P<0.001）。高POR 4和低miR-219表达与间充质GBM亚型显著相关（P<0.0001）。在这里，我们提出了一种新的诊断方法来筛选分子癌症亚型和细胞侵袭的基因组相关性。我们的发现也具有潜在的治疗意义，因为成功的分子抑制侵袭将改善GBM的治疗和患者生存。
Despite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM. Thus, our radiogenomic screen has the potential to reveal novel molecular determinants of invasion. Here, we present the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM. Based on The Cancer Genome Atlas (TCGA), discovery and validation sets with gene, microRNA, and quantitative MR-imaging data were created. Top concordant genes and microRNAs correlated with high FLAIR volumes from both sets were further characterized by Kaplan Meier survival statistics, microRNA-gene correlation analyses, and GBM molecular subtype-specific distribution. The top upregulated gene in both the discovery (4 fold) and validation (11 fold) sets was PERIOSTIN (POSTN). The top downregulated microRNA in both sets was miR-219, which is predicted to bind to POSTN. Kaplan Meier analysis demonstrated that above median expression of POSTN resulted in significantly decreased survival and shorter time to disease progression (P<0.001). High POSTN and low miR-219 expression were significantly associated with the mesenchymal GBM subtype (P<0.0001). Here, we propose a novel diagnostic method to screen for molecular cancer subtypes and genomic correlates of cellular invasion. Our findings also have potential therapeutic significance since successful molecular inhibition of invasion will improve therapy and patient survival in GBM.
登录
查看更多内容
影响因子：
37.3
作者：
Mikheeva SA;Mikheev AM;Petit A;Beyer R;Oxford RG;Khorasani L;Maxwell JP;Glackin CA;Wakimoto H;González-Herrero I;Sánchez-García I;Silber JR;Horner PJ;Rostomily RC
通讯作者：
Rostomily RC
影响因子：
11.2
作者：
Lim, Philip K.;Bliss, Sarah A.;Rameshwar, Pranela
通讯作者：
Rameshwar, Pranela
影响因子：
6.4
作者：
Kanno, Atsushi;Satoh, Kennichi;Shimosegawa, Tooru
通讯作者：
Shimosegawa, Tooru
影响因子：
3
作者：
Gottlieb A;Varshavsky R;Linial M;Horn D
通讯作者：
Horn D
影响因子：
158.5
作者：
Hegi, ME;Diserens, A;Stupp, R
通讯作者：
Stupp, R