Genetic markers and canonical pathways associated with medulloblastoma: a systematic review and meta-analysis.
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BACKGROUND: Medulloblastoma is the most common malignant brain tumor of childhood, accounting for 25% of pediatric central nervous system (CNS) neoplasms. Although the cause of medulloblastoma is unclear, recent findings have contributed to treatment guidelines that emphasize the extent of disease, tumor resection margins, and age of onset. This study synthesizes available evidence to provide further insight into associated genetic markers and associated pathways that may be leveraged for individualized therapy. METHODS: The Search Tag Analyze Resource for NCBI's Gene Expression Omnibus (STARGEO) was utilized to identify 480 medulloblastoma tumor samples and 62 healthy adult and pediatric cerebellum samples. Pathway analysis was conducted using Ingenuity Pathway Analysis (IPA) and restricted to genes with a statistically significant difference (P<0.05) between medulloblastoma and control and an absolute experimental log ratio greater than 0.2. RESULTS: Overall, 4,142 genes met the inclusion criteria. Genes previously described in the context of medulloblastoma, such as SOX11, TBR1, VSNL1, PVALB, as well as novel gene targets such as LHX2, UBE2C and HEPACAM were among the differentially expressed genes identified. The top canonical pathways associated with medulloblastoma were cell cycle checkpoints, synaptogenesis signaling and pathway, mitotic metaphase and anaphase, glutaminergic receptor signaling pathway, and mitotic prophase. The top upstream regulators were beta-estradiol, TP53, HTT, TBX3, and TGFB1. Some of the diseases and biological functions predicted as activated with medulloblastoma based on the differential genetic expression include motor dysfunction or movement disorder and cell proliferation of tumor cell lines, whereas those predicted as inhibited include coordination and misalignment of chromosomes. CONCLUSIONS: Utilizing STARGEO is an effective method for leveraging genomics metadata to highlight novel and previously described pathways and regulators associated with medulloblastoma. By providing an enhanced understanding of the pathophysiology of medulloblastoma, this study provides a framework for future validation studies-the next step toward identifying target genes and biomarkers for screening, prognostication, and targeted treatment for medulloblastoma.