TGIF2 is a potential biomarker for diagnosis and prognosis of glioma
BackgroundTGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its prognostic significance in glioma, impact on tumor immune infiltration, and underlying mechanisms in glioma development...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1356833/full |
| _version_ | 1827297934741340160 |
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| author | Wan Zhang Wan Zhang Long Zhang Huanhuan Dong Hang Peng Hang Peng |
| author_facet | Wan Zhang Wan Zhang Long Zhang Huanhuan Dong Hang Peng Hang Peng |
| author_sort | Wan Zhang |
| collection | DOAJ |
| description | BackgroundTGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its prognostic significance in glioma, impact on tumor immune infiltration, and underlying mechanisms in glioma development remain elusive.MethodsThe expression of TGIF2 in various human normal tissues, normal brain tissues, and gliomas was investigated using HPA, TCGA, GTEx, and GEO databases. The study employed several approaches, including Kaplan-Meier analysis, ROC analysis, logistic regression, Cox regression, GO analysis, KEGG analysis, and GSEA, to explore the relationship between TGIF2 expression and clinicopathologic features, prognostic value, and potential biological functions in glioma patients. The impact of TGIF2 on tumor immune infiltration was assessed through Estimate, ssGSEA, and Spearman analysis. Genes coexpressed with TGIF2 were identified, and the protein-protein interaction (PPI) network of these coexpressed genes were constructed using the STRING database and Cytoscape software. Hub genes were identified using CytoHubba plugin, and their clinical predictive value was explored. Furthermore, in vitro experiments were performed by knocking down and knocking out TGIF2 using siRNA and CRISPR/Cas9 gene editing, and the role of TGIF2 in glioma cell invasion and migration was analyzed using transwell assay, scratch wound-healing assay, RT-qPCR, and Western blot.ResultsTGIF2 mRNA was found to be upregulated in 21 cancers, including glioma. High expression of TGIF2 was associated with malignant phenotypes and poor prognosis in glioma patients, indicating its potential as an independent prognostic factor. Furthermore, elevated TGIF2 expression positively correlated with cell cycle regulation, DNA synthesis and repair, extracellular matrix (ECM) components, immune response, and several signaling pathways that promote tumor progression. TGIF2 showed correlations with Th2 cells, macrophages, and various immunoregulatory genes. The hub genes coexpressed with TGIF2 demonstrated significant predictive value. Additionally, in vitro experiments revealed that knockdown and knockout of TGIF2 inhibited glioma cell invasion, migration and suppressed the epithelial-mesenchymal transition (EMT) phenotype.ConclusionTGIF2 emerges as a potential biomarker for glioma, possibly linked to tumor immune infiltration and EMT. |
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| format | Article |
| id | doaj.art-b2d180ffdeee4ae4a018f491357c623b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T15:05:17Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-b2d180ffdeee4ae4a018f491357c623b2024-04-02T13:30:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13568331356833TGIF2 is a potential biomarker for diagnosis and prognosis of gliomaWan Zhang0Wan Zhang1Long Zhang2Huanhuan Dong3Hang Peng4Hang Peng5Health Science Center of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaBone and Joints Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaHealth Science Center of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaSecond Department of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, ChinaBackgroundTGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its prognostic significance in glioma, impact on tumor immune infiltration, and underlying mechanisms in glioma development remain elusive.MethodsThe expression of TGIF2 in various human normal tissues, normal brain tissues, and gliomas was investigated using HPA, TCGA, GTEx, and GEO databases. The study employed several approaches, including Kaplan-Meier analysis, ROC analysis, logistic regression, Cox regression, GO analysis, KEGG analysis, and GSEA, to explore the relationship between TGIF2 expression and clinicopathologic features, prognostic value, and potential biological functions in glioma patients. The impact of TGIF2 on tumor immune infiltration was assessed through Estimate, ssGSEA, and Spearman analysis. Genes coexpressed with TGIF2 were identified, and the protein-protein interaction (PPI) network of these coexpressed genes were constructed using the STRING database and Cytoscape software. Hub genes were identified using CytoHubba plugin, and their clinical predictive value was explored. Furthermore, in vitro experiments were performed by knocking down and knocking out TGIF2 using siRNA and CRISPR/Cas9 gene editing, and the role of TGIF2 in glioma cell invasion and migration was analyzed using transwell assay, scratch wound-healing assay, RT-qPCR, and Western blot.ResultsTGIF2 mRNA was found to be upregulated in 21 cancers, including glioma. High expression of TGIF2 was associated with malignant phenotypes and poor prognosis in glioma patients, indicating its potential as an independent prognostic factor. Furthermore, elevated TGIF2 expression positively correlated with cell cycle regulation, DNA synthesis and repair, extracellular matrix (ECM) components, immune response, and several signaling pathways that promote tumor progression. TGIF2 showed correlations with Th2 cells, macrophages, and various immunoregulatory genes. The hub genes coexpressed with TGIF2 demonstrated significant predictive value. Additionally, in vitro experiments revealed that knockdown and knockout of TGIF2 inhibited glioma cell invasion, migration and suppressed the epithelial-mesenchymal transition (EMT) phenotype.ConclusionTGIF2 emerges as a potential biomarker for glioma, possibly linked to tumor immune infiltration and EMT.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1356833/fullTGIF2biomarkergliomaimmune infiltrationEMT |
| spellingShingle | Wan Zhang Wan Zhang Long Zhang Huanhuan Dong Hang Peng Hang Peng TGIF2 is a potential biomarker for diagnosis and prognosis of glioma Frontiers in Immunology TGIF2 biomarker glioma immune infiltration EMT |
| title | TGIF2 is a potential biomarker for diagnosis and prognosis of glioma |
| title_full | TGIF2 is a potential biomarker for diagnosis and prognosis of glioma |
| title_fullStr | TGIF2 is a potential biomarker for diagnosis and prognosis of glioma |
| title_full_unstemmed | TGIF2 is a potential biomarker for diagnosis and prognosis of glioma |
| title_short | TGIF2 is a potential biomarker for diagnosis and prognosis of glioma |
| title_sort | tgif2 is a potential biomarker for diagnosis and prognosis of glioma |
| topic | TGIF2 biomarker glioma immune infiltration EMT |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1356833/full |
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