We investigated the transcription of circadian clock genes in publicly available datasets of gene expression in medulloblastoma (MB) tissues using the R2 Genomics Analysis and Visualization Platform. Differential expression of the core clock genes among the four consensus subgroups of MB (defined in 2012 as Group 3, Group 4, the SHH group, and the WNT group) included the core clock genes (CLOCK,NPAS2,PER1,PER2,CRY1, CRY2,BMAL1,BMAL2,NR1D1, andTIMELESS) and genes which encode proteins that regulate the transcription of clock genes (CIPC,FBXL21, andUSP2). The over-expression of several clock genes, includingCIPC, was found in individuals with the isochromosome 17q chromosomal aberration in MB Group 3 and Group 4. The most significant biological pathways associated with clock gene expression wereribosome subunits,phototransduction,GABAergic synapse,WNT signaling pathway, and theFanconi anemia pathway. Survival analysis of clock genes was examined using the Kaplan–Meier method and the Cox proportional hazards regression model through the R2 Genomics Platform. Two clock genes most significantly related to survival wereCRY1andUSP2. The data suggest that several clock proteins, includingCRY1andUSP2, be investigated as potential therapeutic targets in MB.
我们利用R2基因组学分析与可视化平台,对公开的髓母细胞瘤组织基因表达数据集中的生物钟基因转录情况进行了研究。在髓母细胞瘤四个共识亚组(2012年定义为第3组、第4组、SHH组和WNT组)中,核心生物钟基因(包括CLOCK、NPAS2、PER1、PER2、CRY1、CRY2、BMAL1、BMAL2、NR1D1和TIMELESS)以及编码调控生物钟基因转录蛋白的基因(CIPC、FBXL21和USP2)存在差异表达。研究发现,在髓母细胞瘤第3组和第4组中携带17号染色体长臂等臂染色体畸变的个体中,包括CIPC在内的多个生物钟基因呈现过表达。与生物钟基因表达最显著相关的生物学通路包括核糖体亚基、光转导、GABA能突触、WNT信号通路以及范可尼贫血通路。通过R2基因组学平台,采用Kaplan-Meier方法和Cox比例风险回归模型对生物钟基因进行了生存分析。与生存相关性最显著的两个生物钟基因为CRY1和USP2。这些数据表明,包括CRY1和USP2在内的多个生物钟蛋白可作为髓母细胞瘤潜在治疗靶点进行深入研究。