Higdon Roger, Kala Jessie, Wilkins Devan, Yan Julia Fangfei, Sethi Manveen K, Lin Liang, Liu Siqi, Montague Elizabeth, Janko Imre, Choiniere John, Kolker Natali, Hancock William S, Kolker Eugene, Fanayan Susan
Bioinformatics and High-Throughput Analysis Laboratory, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Data and Analytics, Seattle Children's Hospital, Seattle, WA 98101, USA.
Proteomes. 2017 Feb 3;5(1):5. doi: 10.3390/proteomes5010005.
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Patient survival has remained largely the same for the past 20 years, with therapies causing significant health, cognitive, behavioral and developmental complications for those who survive the tumor. In this study, we profiled the total transcriptome and proteome of two established MB cell lines, Daoy and UW228, using high-throughput RNA sequencing (RNA-Seq) and label-free nano-LC-MS/MS-based quantitative proteomics, coupled with advanced pathway analysis. While Daoy has been suggested to belong to the sonic hedgehog (SHH) subtype, the exact UW228 subtype is not yet clearly established. Thus, a goal of this study was to identify protein markers and pathways that would help elucidate their subtype classification. A number of differentially expressed genes and proteins, including a number of adhesion, cytoskeletal and signaling molecules, were observed between the two cell lines. While several cancer-associated genes/proteins exhibited similar expression across the two cell lines, upregulation of a number of signature proteins and enrichment of key components of SHH and WNT signaling pathways were uniquely observed in Daoy and UW228, respectively. The novel information on differentially expressed genes/proteins and enriched pathways provide insights into the biology of MB, which could help elucidate their subtype classification.
髓母细胞瘤（MB）是最常见的儿童恶性脑肿瘤。在过去20年里，患者生存率基本保持不变，而治疗方法却给那些肿瘤幸存者带来了严重的健康、认知、行为和发育并发症。在本研究中，我们使用高通量RNA测序（RNA-Seq）和基于无标记纳米液相色谱-串联质谱的定量蛋白质组学，并结合先进的通路分析，对两种已建立的MB细胞系Daoy和UW228的全转录组和蛋白质组进行了分析。虽然有人认为Daoy属于音猬因子（SHH）亚型，但UW228的确切亚型尚未明确确定。因此，本研究的一个目标是鉴定有助于阐明其亚型分类的蛋白质标志物和通路。在这两种细胞系之间观察到了许多差异表达的基因和蛋白质，包括一些黏附、细胞骨架和信号分子。虽然有几个癌症相关基因/蛋白质在两种细胞系中表现出相似的表达，但分别在Daoy和UW228中独特地观察到了一些标志性蛋白质的上调以及SHH和WNT信号通路关键成分的富集。关于差异表达基因/蛋白质和富集通路的新信息为MB的生物学特性提供了见解，这有助于阐明它们的亚型分类。
