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Genetic Profiles Playing Opposite Roles of Pathogenesis in Schizophrenia and Glioma.

ABSTRACT: Background:Patients diagnosed with schizophrenia were found having lower risks to develop cancers, including glioma. Based on this epidemiology, we hypothesized that there were gene profiles playing opposite roles in pathogenesis of schizophrenia and glioma. Methods:Based on GEO datasets and TCGA, key genes of schizophrenia genes on the opposite development of glioma were screened by different expressed genes (DEGs) screening, weighted gene coexpression network analysis (WGCNA), disease-specific survival (DSS), and glioma grading and verified by gene set enrichment analysis (GSEA). Results:First, 612 DEGs were screened from schizophrenia and control brain samples. Second, 134 key genes more specific to schizophrenia were left by WGCNA, with 93 key genes having annotations in TCGA. Third, DSS of glioma helped to find 42 key gene expressions of schizophrenia oppositely associated with survival of glioma. Finally, 24 key genes showed opposite expression trends in schizophrenia and different glioma grading, i.e., the upregulated key genes in schizophrenia expressed increasingly in higher grade glioma, and vice versa. CAMK2D and MPC2 were taken as the examples and evaluated by GSEA, which indeed showed opposite trends in the same pathways of schizophrenia and glioma. Conclusion:This workflow of selecting novel targeted genes which may have opposite roles in pathogenesis of two diseases was firstly and innovatively generated by our team. Some filtered key genes were indeed found by their potential effects in several mechanism studies, indicating our process could be effective to generate novel targeted genes. These 24 key genes may provide potential directions for future biochemical and pharmacotherapeutic research studies.

SUBMITTER: Wen YD

PROVIDER: S-EPMC7275202 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genetic Profiles Playing Opposite Roles of Pathogenesis in Schizophrenia and Glioma.

Wen Ya-Dan YD Xia Zhi-Wei ZW Li Dong-Jie DJ Cheng Quan Q Zhao Qing Q Cao Hui H

Journal of oncology 20200528

<h4>Background</h4>Patients diagnosed with schizophrenia were found having lower risks to develop cancers, including glioma. Based on this epidemiology, we hypothesized that there were gene profiles playing opposite roles in pathogenesis of schizophrenia and glioma.<h4>Methods</h4>Based on GEO datasets and TCGA, key genes of schizophrenia genes on the opposite development of glioma were screened by different expressed genes (DEGs) screening, weighted gene coexpression network analysis (WGCNA), d ...[more]

PMID: 32565801

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Project description:Glioma is the most common malignant brain tumor, and the incidence of glioma demonstrates an upward trend. It is vital to elucidate the pathogenesis of glioma and seek effective therapies. The aim of the present study was to identify the potential gene markers associated with glioma based on GSE31262 gene expression profiles, and to explore the underlying mechanism of glioma progression by analyzing the gene markers. The microarray dataset GSE31262 was downloaded and neural stem cell samples (control group) and glioma samples (glioma group) were analyzed to identify the differentially expressed genes (DEGs) between the two groups. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using DAVID software. Subsequently, a protein‑protein interaction (PPI) network was constructed and important modules were extracted from this network. Additionally, the miRNA‑target regulatory network was established. In total, 1377 DEGs with P<0.01 and |log2 fold change| ≥2 were identified between the control and glioma groups. The DEGs that were upregulated in glioma samples compared with controls were primarily associated with functions such as the M phase and cell cycle pathway, while the downregulated genes were associated with functions such as nerve impulse and the axon guidance pathway. The results also indicated that certain DEGs, including cyclin‑dependent kinase 1 (CDK1) and cadherin 1 (CDH1), had important roles in the PPI network. The MCODE tool in Cytoscape software was used to identify upregulated and downregulated modules in the PPI network, and 5 upregulated and 2 downregulated modules were extracted. Furthermore, the WebGestal online tool was used to identify potential interactions of the upregulated and downregulated genes with microRNAs (miRNA/miR), and miR‑135A/B and its two targets, discs large MAGUK scaffold protein 2 and forkhead box O1 (FOXO1), had the highest number of connections in the miRNA‑target regulatory network. In addition, cell division cycle 20 and FOXO1 were confirmed to be upregulated in U87 glioma cells compared with normal human astrocytes (HA1800) by reverse transcription‑quantitative polymerase chain reaction. In conclusion, M phase function and the axon guidance pathway may be vital for glioma progression. In addition, CDK1 and CDH1 may be associated with the process of glioma. Furthermore, miR‑135A/B, and the target FOXO1, may be potential therapy targets for glioma treatment.

Dataset Information

Genetic Profiles Playing Opposite Roles of Pathogenesis in Schizophrenia and Glioma.

Publications

Genetic Profiles Playing Opposite Roles of Pathogenesis in Schizophrenia and Glioma.

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