Abstract
Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis. The main finding was the identification of five hub genes from the WNT subgroup that are tumor suppressors, and whose lower expression is related to a worse prognosis for MB patients. Furthermore, the common genes correlated with the five tumor suppressors participate in important pathways and processes for tumor initiation and progression, as well as development and differentiation, and some of them control cell stemness and pluripotency. These genes have not yet been studied within the context of MB, representing new important elements for investigation in the search for therapeutic targets, prognostic markers or for understanding of MB biology.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. All data presented in this study are available.
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Acknowledgements
This work was financially supported by FAPESP n. 2014/20341-0 and CAPES n. 88882.317618/2019-01.
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The funded was provided by fundação de amparo à pesquisa do estado de são Paulo, Grant No. (2014/20341-0), coordenação de aperfeiçoamento de pessoal de nível superior, Grant No. (88882.317618/2019-01).
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AMS and MB planned and conducted data analysis and drafted the manuscript. KBS, PFC, RBS, LG and GAVC wrote and organized the data, created the figures/tables, and edited and finalized the manuscript. CAPC and RGPQ helpful in preliminary experiments. WASJ, SKNM, SRB, JAY, CGCJ, CAS, ETV and LGT revised the text for important intellectual content. All authors confirm that this manuscript has not been previously published and is not currently under consideration by any other journal.
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Figure S1. Representative figure of eight WNT clusters (A-H) with hub genes identified by CytoHubba analysis. (Supplementary table 1 showed correspondent score and rank values) (PDF 102 kb)
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Figure S2. Representative figure of three SHH clusters (A-C) with hub genes identified by CytoHubba analysis. (Supplementary table 2 showed correspondent score and rank values) (PDF 53 kb)
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Figure S3. Representative figure of one Grp-3 cluster (A) with hub genes identified by CytoHubba analysis. (Supplementary table 3 showed correspondent score and rank values) (PDF 18 kb)
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Figure S4. Representative figure of one Grp-4 cluster (A) with hub genes identified by CytoHubba analysis. (Supplementary table 4 showed correspondent score and rank values) (PDF 14 kb)
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Figure S5. Expression pattern of the LEF1 (A), WIF1 (B), AXIN2 (C), EPHA3 (D) and GALR1 (E) hub gene between the MB molecular subgroups from four data sets with GSE181293 (17 samples), GSE85217 (643 samples), GSE37418 (73 samples) and EGAS00001001953 (186 samples). The expression data of pediatric patients were obtained from R2: Genomics Analysis and Visualization Platform with the censoring of data from 0 to 19-year-old patients (PDF 199 kb)
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Martins-da-Silva, A., Baroni, M., Salomão, K.B. et al. Clinical Prognostic Implications of Wnt Hub Genes Expression in Medulloblastoma. Cell Mol Neurobiol 43, 813–826 (2023). https://doi.org/10.1007/s10571-022-01217-4
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DOI: https://doi.org/10.1007/s10571-022-01217-4