Abstract
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.
Highlights
Medulloblastoma (MB) is the most common malignant brain tumor, with a greater incidence (10–20 times) in young people under 20 years of age [1,2]
Proteomic data from Daoy and UW228 cell lines were compared to each other to identify potential signature proteins and pathways, which could help distinguish between these two cell lines
The complete list of proteins included additional 1543 proteins in Daoy and 1337 proteins in UW228, identified with only one unique peptide, which were excluded from the subsequent analysis
Summary
Medulloblastoma (MB) is the most common malignant brain tumor, with a greater incidence (10–20 times) in young people under 20 years of age [1,2]. Kool et al, through a meta-analysis of all available molecular and clinical data for medulloblastoma, identified four consistent core molecular subgroups of medulloblastoma across all published datasets with distinct clinical, genetic and prognostic features [10]. These combined efforts resulted in a consensus at a recent conference in Boston in 2010, supporting the classification of medulloblastomas, based on the molecular profiling, into four clinical and molecular subtypes: the WNT subtype, in which the canonical WNT signaling is upregulated; the sonic hedgehog (SHH)
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