Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma
IntroductionTransferrin receptor protein 1 (TFRC), an ananda molecule associated with ferroptosis, has been identified as affecting a wide spectrum of pathological processes in various cancers, but the prognostic value correlates with the tumor microenvironment of TFRC in lower-grade glioma (LGG) is...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.972308/full |
| _version_ | 1811318941404889088 |
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| author | Hongrong Wu Haoyang He Jiexiong Huang Chuan Wang Yuejiao Dong Ruilin Lin Zhuofeng Cheng Qiancheng Qiu LiangLi Hong |
| author_facet | Hongrong Wu Haoyang He Jiexiong Huang Chuan Wang Yuejiao Dong Ruilin Lin Zhuofeng Cheng Qiancheng Qiu LiangLi Hong |
| author_sort | Hongrong Wu |
| collection | DOAJ |
| description | IntroductionTransferrin receptor protein 1 (TFRC), an ananda molecule associated with ferroptosis, has been identified as affecting a wide spectrum of pathological processes in various cancers, but the prognostic value correlates with the tumor microenvironment of TFRC in lower-grade glioma (LGG) is still unclear.Materials and methodsClinical pathological information and gene expression data of patients with LGG come from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GTEx, Oncomine, UCSC Xena, and GEO databases. We then used various bioinformatics methods and mathematical models to analyze those data, aiming to investigate the clinical significance of TFRC in LGG and illustrate its association with tumor immunity. In addition, the molecular function and mechanisms of TFRC were revealed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Immunohistochemical experiments and single-cell analysis have been performed.ResultsTFRC expression was highly expressed in many tumors and showed a poor prognosis. Including gliomas, it was significantly associated with several poor clinical prognostic variables, tumor immune microenvironment, tumor mutational burden (TMB), m6a modification, and ferroptosis in LGG. TFRC as a key factor was further used to build a prediction nomogram. The C-index, calibration curve, and decision curve analysis showed the nomogram was clinically useful and calibration was accurate. At the same time, we also demonstrated that promoter hypomethylation of DNA upstream of TFRC could lead to high TFRC expression and poor overall survival. There is a significant correlation between TFRC and CD8 + T cell, macrophage cell infiltration, and several immune checkpoints, such as PD-L1(cd274), CTLA4, and PD1, suggesting a novel direction for future clinical application. Functional and molecular mechanism analysis showed an association of TFRC expression with immune-related pathways through GSEA, GO, and KEGG analysis. Finally, immunohistochemical experiments and single-cell analysis confirmed the expression of TFRC in glioma.ConclusionTFRC may be a potential prognostic biomarker and an immunotherapeutic target for glioma. |
| first_indexed | 2024-04-13T12:33:55Z |
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| language | English |
| last_indexed | 2024-04-13T12:33:55Z |
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| spelling | doaj.art-ca555c81f04245179d376f560616870d2022-12-22T02:46:43ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-11-011510.3389/fnmol.2022.972308972308Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade gliomaHongrong Wu0Haoyang He1Jiexiong Huang2Chuan Wang3Yuejiao Dong4Ruilin Lin5Zhuofeng Cheng6Qiancheng Qiu7LiangLi Hong8Department of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaThe First Clinical Medical College of Guangdong Medical University, Zhanjiang, Guangdong, ChinaDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaIntroductionTransferrin receptor protein 1 (TFRC), an ananda molecule associated with ferroptosis, has been identified as affecting a wide spectrum of pathological processes in various cancers, but the prognostic value correlates with the tumor microenvironment of TFRC in lower-grade glioma (LGG) is still unclear.Materials and methodsClinical pathological information and gene expression data of patients with LGG come from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GTEx, Oncomine, UCSC Xena, and GEO databases. We then used various bioinformatics methods and mathematical models to analyze those data, aiming to investigate the clinical significance of TFRC in LGG and illustrate its association with tumor immunity. In addition, the molecular function and mechanisms of TFRC were revealed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Immunohistochemical experiments and single-cell analysis have been performed.ResultsTFRC expression was highly expressed in many tumors and showed a poor prognosis. Including gliomas, it was significantly associated with several poor clinical prognostic variables, tumor immune microenvironment, tumor mutational burden (TMB), m6a modification, and ferroptosis in LGG. TFRC as a key factor was further used to build a prediction nomogram. The C-index, calibration curve, and decision curve analysis showed the nomogram was clinically useful and calibration was accurate. At the same time, we also demonstrated that promoter hypomethylation of DNA upstream of TFRC could lead to high TFRC expression and poor overall survival. There is a significant correlation between TFRC and CD8 + T cell, macrophage cell infiltration, and several immune checkpoints, such as PD-L1(cd274), CTLA4, and PD1, suggesting a novel direction for future clinical application. Functional and molecular mechanism analysis showed an association of TFRC expression with immune-related pathways through GSEA, GO, and KEGG analysis. Finally, immunohistochemical experiments and single-cell analysis confirmed the expression of TFRC in glioma.ConclusionTFRC may be a potential prognostic biomarker and an immunotherapeutic target for glioma.https://www.frontiersin.org/articles/10.3389/fnmol.2022.972308/fullTFRCLGGprognosistumor microenvironmentferroptosis |
| spellingShingle | Hongrong Wu Haoyang He Jiexiong Huang Chuan Wang Yuejiao Dong Ruilin Lin Zhuofeng Cheng Qiancheng Qiu LiangLi Hong Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma Frontiers in Molecular Neuroscience TFRC LGG prognosis tumor microenvironment ferroptosis |
| title | Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma |
| title_full | Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma |
| title_fullStr | Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma |
| title_full_unstemmed | Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma |
| title_short | Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma |
| title_sort | identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma |
| topic | TFRC LGG prognosis tumor microenvironment ferroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.972308/full |
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