Identification of ITPR1 as a Hub Gene of Group 3 Medulloblastoma and Coregulated Genes with Potential Prognostic Values

Author(s):Show less -

das Chagas, Pablo Ferreira ^[1] ; de Sousa, Graziella Ribeiro ^[1] ; Veronez, Luciana Chain ^[2] ; Martins-da-Silva, Andrea ^[2] ; Correa, Carolina Alves Pereira ^[1] ; Cruzeiro, Gustavo Alencastro Veiga ^{[3, 2, 4]} ; Nagano, Luis Fernando Peinado ^[1] ; Queiroz, Rosane Gomes de Paula ^[2] ; Marie, Suely Kazue Nagahashi ^[5] ; Brandalise, Silvia Regina ^[6] ; Scrideli, Carlos Alberto ^{[1, 2]} ; Tone, Luiz Gonzaga ^{[1, 2]} ; Valera, Elvis Terci ^[2]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ave Bandeirantes, BR-39001404 Ribeirao Preto - Brazil

^[2] Univ Sao Paulo Ribeirao Preto, Ribeirao Preto Med Sch, Clin Hosp, Dept Pediat, Ribeirao Preto - Brazil

^[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 - USA

^[4] Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA - USA

^[5] Fac Med FMUSP Univ Sao Paulo, Dept Neurol, Lab Cellular & Mol Biol, Sao Paulo, SP - Brazil

^[6] Boldrinis Children Ctr, Campinas, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF MOLECULAR NEUROSCIENCE; NOV 2021.
• Web of Science Citations: 0

Abstract

The Group 3 Medulloblastoma (Grp3-MB) is an aggressive molecular subtype with a high incidence of metastasis and deaths. In this study, were used an RNA sequencing data (RNA-Seq) from a Brazilian cohort of MBs to identify hub genes associated with the metastatic risk. Data validation were performed by using multiple large datasets from MBs (GSE85217, GSE37418, and EGAS00001001953). DESeq2 package in R software was used to identify the differentially expressed genes (DEGs) in our RNA-Seq data. The DEGs data were accessed to construct the modules/graphs of co-expression and to identify hub genes through Cytoscape platform. The coregulated genes were enriched by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) network was visualized by Cytoscape. The Kaplan-Meier plotter and ROC curves were used to validate the diagnostic and prognostic values of specific biomarkers identified through this model. We identified that inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) as a downregulated hub gene, with a high diagnostic accuracy to Grp3-MBs and associated with tumor metastasis. In addition, we identified genes significantly correlated with ITPR1 that were associated with metastasis in Grp3-MB (ATP1A2, MTTL7A, and RGL1) and worst overall survival in MBs (ANTXR1 and RGL1). Our findings suggest that the ITPR1 hub gene is potentially involved in the metastatic process for Grp3-MB. Our data also provide evidence of targets that may serve as prognostic predictors and/or regulators for the metastatic process that maybe explored for further research of individualized therapy to Grp3-MBs. (AU)

• FAPESP's process: 17/26160-5 - Musashi-1 gene in medulloblastoma group 3 and 4
• Grantee: Pablo Shimaoka Chagas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/20341-0 - Interactions between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on pediatric malignancies
• Grantee: Luiz Gonzaga Tone
• Support Opportunities: Research Projects - Thematic Grants