An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas
Abstract Background Lack of knowledge around underlying mechanisms of gliomas mandates intense research efforts to improve the disease outcomes. Identification of high-grade gliomas pathogenesis which is known for poor prognosis and low survival is of particular importance. Distinguishing the differ...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Diagnostic Pathology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13000-022-01253-0 |
| _version_ | 1798001621870837760 |
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| author | Reza Ahmadi-Beni Shirin Shahbazi Alireza Khoshnevisan |
| author_facet | Reza Ahmadi-Beni Shirin Shahbazi Alireza Khoshnevisan |
| author_sort | Reza Ahmadi-Beni |
| collection | DOAJ |
| description | Abstract Background Lack of knowledge around underlying mechanisms of gliomas mandates intense research efforts to improve the disease outcomes. Identification of high-grade gliomas pathogenesis which is known for poor prognosis and low survival is of particular importance. Distinguishing the differentially expressed genes is one of the core approaches to clarify the causative factors. Methods Microarray datasets of the treatment-naïve gliomas were provided from the Gene Expression Omnibus considering the similar platform and batch effect removal. Interacting recovery of the top differentially expressed genes was performed on the STRING and Cytoscape platforms. Kaplan–Meier analysis was piloted using RNA sequencing data and the survival rate of glioma patients was checked considering selected genes. To validate the bioinformatics results, the gene expression was elucidated by real-time RT-qPCR in a series of low and high-grade fresh tumor samples. Results We identified 323 up-regulated and 253 down-regulated genes. The top 20 network analysis indicated that PTX3, TIMP1, CHI3L1, LTF and IGFBP3 comprise a crucial role in gliomas progression. The survival was inversely linked to the levels of all selected genes. Further analysis of RNA sequencing data indicated a significant increase in all five genes in high-grade tumors. Among them, PTX3, TIMP1 and LTF did not show any change in low-grade versus controls. Real-time RT-qPCR confirmed the in-silico results and revealed significantly higher expression of selected genes in high-grade samples compared to low-grade. Conclusions Our results highlighted the role of PTX3 and TIMP1 which were previously considered in glioma tumorigenesis as well as LTF as a new potential biomarker. |
| first_indexed | 2024-04-11T11:39:02Z |
| format | Article |
| id | doaj.art-7c9662a4df9c44e18c0639e4f05841bb |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-04-11T11:39:02Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic Pathology |
| spelling | doaj.art-7c9662a4df9c44e18c0639e4f05841bb2022-12-22T04:25:52ZengBMCDiagnostic Pathology1746-15962022-09-0117111010.1186/s13000-022-01253-0An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomasReza Ahmadi-Beni0Shirin Shahbazi1Alireza Khoshnevisan2Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares UniversityDepartment of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares UniversityDepartment of Neurosurgery, Shariati Hospital, Tehran University of Medical SciencesAbstract Background Lack of knowledge around underlying mechanisms of gliomas mandates intense research efforts to improve the disease outcomes. Identification of high-grade gliomas pathogenesis which is known for poor prognosis and low survival is of particular importance. Distinguishing the differentially expressed genes is one of the core approaches to clarify the causative factors. Methods Microarray datasets of the treatment-naïve gliomas were provided from the Gene Expression Omnibus considering the similar platform and batch effect removal. Interacting recovery of the top differentially expressed genes was performed on the STRING and Cytoscape platforms. Kaplan–Meier analysis was piloted using RNA sequencing data and the survival rate of glioma patients was checked considering selected genes. To validate the bioinformatics results, the gene expression was elucidated by real-time RT-qPCR in a series of low and high-grade fresh tumor samples. Results We identified 323 up-regulated and 253 down-regulated genes. The top 20 network analysis indicated that PTX3, TIMP1, CHI3L1, LTF and IGFBP3 comprise a crucial role in gliomas progression. The survival was inversely linked to the levels of all selected genes. Further analysis of RNA sequencing data indicated a significant increase in all five genes in high-grade tumors. Among them, PTX3, TIMP1 and LTF did not show any change in low-grade versus controls. Real-time RT-qPCR confirmed the in-silico results and revealed significantly higher expression of selected genes in high-grade samples compared to low-grade. Conclusions Our results highlighted the role of PTX3 and TIMP1 which were previously considered in glioma tumorigenesis as well as LTF as a new potential biomarker.https://doi.org/10.1186/s13000-022-01253-0Adult gliomaIntegrated bioinformaticsGEO dataDifferentially expressed genes |
| spellingShingle | Reza Ahmadi-Beni Shirin Shahbazi Alireza Khoshnevisan An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas Diagnostic Pathology Adult glioma Integrated bioinformatics GEO data Differentially expressed genes |
| title | An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas |
| title_full | An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas |
| title_fullStr | An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas |
| title_full_unstemmed | An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas |
| title_short | An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas |
| title_sort | integrative bioinformatics investigation and experimental validation of critically involved genes in high grade gliomas |
| topic | Adult glioma Integrated bioinformatics GEO data Differentially expressed genes |
| url | https://doi.org/10.1186/s13000-022-01253-0 |
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