Identification of hub genes and small-molecule compounds in medulloblastoma by integrated bioinformatic analyses

Zhendong Liu; Ruotian Zhang; Zhenying Sun; Jiawei Yao; Penglei Yao; Xin Chen; Xinzhuang Wang; Ming Gao; Jinzhao Wan; Yiming Du; Shiguang Zhao

doi:10.7717/peerj.8670

Identification of hub genes and small-molecule compounds in medulloblastoma by integrated bioinformatic analyses

PeerJ. 2020 Apr 14:8:e8670. doi: 10.7717/peerj.8670. eCollection 2020.

Authors

Zhendong Liu^#^{1

2}, Ruotian Zhang^#^{1

2}, Zhenying Sun^{1

2}, Jiawei Yao^{1

2}, Penglei Yao^{1

2}, Xin Chen^{1

2}, Xinzhuang Wang^{1

2}, Ming Gao^{1

2}, Jinzhao Wan^{1

2}, Yiming Du^{1

2}, Shiguang Zhao^{1

2}

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
² Institute of Brain Science, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.

^# Contributed equally.

Abstract

Background: Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We aimed to identify potential biomarkers and small-molecule drugs for MB.

Methods: Gene expression profile data sets were obtained from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using the Limma package in R. Functional annotation, and cell signaling pathway analysis of DEGs was carried out using DAVID and Kobas. A protein-protein interaction network was generated using STRING. Potential small-molecule drugs were identified using CMap.

Result: We identified 104 DEGs (29 upregulated; 75 downregulated). Gene ontology analysis showed enrichment in the mitotic cell cycle, cell cycle, spindle, and DNA binding. Cell signaling pathway analysis identified cell cycle, HIF-1 signaling pathway, and phospholipase D signaling pathway as key pathways. SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were the prominent hub genes and their expression level were verified by RT-qPCR. Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB. The five hub genes may be targets for diagnosis and treatment of MB, and the small-molecule compounds are promising drugs for effective treatment of MB.

Conclusion: In this study we obtained five hub genes of MB, SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were confirmed as hub genes. Meanwhile, Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB.

Keywords: Bioinformatical analysis; Differentially expressed genes; Medulloblastoma; Small-molecule drugs.

Grants and funding

This study was supported by the Special Fund for Translational Research of Sino-Russia Medical Research Center in Harbin Medical University (CR201410, CR201512). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.