Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma
Abstract Objective This study aims to build a prognostic model of hepatocellular carcinoma (HCC) with ferroptosis-associated genes and explore their molecular function. Methods Gene expression data and clinical information were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome At...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2023-05-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-023-00677-4 |
| _version_ | 1827943365023367168 |
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| author | Qixian Wu Zhenlin Tan Yu Xiong Chengxin Gu Jingdon Zhou Hui Yang Jiyuan Zhou |
| author_facet | Qixian Wu Zhenlin Tan Yu Xiong Chengxin Gu Jingdon Zhou Hui Yang Jiyuan Zhou |
| author_sort | Qixian Wu |
| collection | DOAJ |
| description | Abstract Objective This study aims to build a prognostic model of hepatocellular carcinoma (HCC) with ferroptosis-associated genes and explore their molecular function. Methods Gene expression data and clinical information were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and the International Cancer Genome Consortium (ICGC). A ferroptosis-associated gene set was obtained from the FerrDb database to identify differentially expressed genes. Then, we performed pathway enrichment analysis and immune infiltration analysis. A combined model based on ferroptosis-associated genes for predicting the overall survival of HCC was built by univariate and multivariate Cox regression analyses. Quantitative real-time polymerase chain reaction, Western blotting, colony formation, CCK-8, and EdU incorporation assays were performed to clarify the function of CAPG in the regulation of cell proliferation in human HCC. Ferroptosis was evaluated by glutathione (GSH), malondialdehyde (MDA), and total iron detection. Results Forty-nine ferroptosis-related genes were significantly correlated with HCC, 19 of which had prognostic significance. CAPG, SLC7A11 and SQSTM1 were used to construct a novel risk model. The areas under the curves (AUCs) were 0.746 and 0.720 (1 year) in the training and validation groups, respectively. The survival analysis indicated that patients with high risk scores exhibited worse survival in the training and validation groups. The risk score was also identified as an independent prognostic factor of overall survival (OS), which established and validated the predictive abilities of the nomogram. The risk score was also significantly correlated with the expression of immune checkpoint genes. In vitro data showed that CAPG knockdown dramatically suppressed HCC cell proliferation, and the underlying molecular mechanisms might be that the silencing of CAPG reduced the expression of SLC7A11 and promoted ferroptosis. Conclusion The established risk model can be used to predict the prognosis of HCC. At the mechanistic level, CAPG may drive HCC progression by regulating SLC7A11, and ferroptosis activation in HCC patients with high CAPG expression may serve as a potential therapeutic strategy. |
| first_indexed | 2024-03-13T10:14:18Z |
| format | Article |
| id | doaj.art-1c0a7c5f5fe2432e9cb8435466f2bf23 |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-03-13T10:14:18Z |
| publishDate | 2023-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-1c0a7c5f5fe2432e9cb8435466f2bf232023-05-21T11:19:43ZengSpringerDiscover Oncology2730-60112023-05-0114111610.1007/s12672-023-00677-4Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinomaQixian Wu0Zhenlin Tan1Yu Xiong2Chengxin Gu3Jingdon Zhou4Hui Yang5Jiyuan Zhou6Department of Gastroenterology, the Second Affiliated Hospital of Guangzhou Medical UniversityDepartment of Gastroenterology, the Second Affiliated Hospital of Guangzhou Medical UniversityIntervention and Cell Therapy Center, Peking University Shenzhen HospitalDepartment of Gastroenterology, the Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityDepartment of Gastroenterology, the Second Affiliated Hospital of Guangzhou Medical UniversityDepartment of Gastroenterology, the Second Affiliated Hospital of Guangzhou Medical UniversityAbstract Objective This study aims to build a prognostic model of hepatocellular carcinoma (HCC) with ferroptosis-associated genes and explore their molecular function. Methods Gene expression data and clinical information were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and the International Cancer Genome Consortium (ICGC). A ferroptosis-associated gene set was obtained from the FerrDb database to identify differentially expressed genes. Then, we performed pathway enrichment analysis and immune infiltration analysis. A combined model based on ferroptosis-associated genes for predicting the overall survival of HCC was built by univariate and multivariate Cox regression analyses. Quantitative real-time polymerase chain reaction, Western blotting, colony formation, CCK-8, and EdU incorporation assays were performed to clarify the function of CAPG in the regulation of cell proliferation in human HCC. Ferroptosis was evaluated by glutathione (GSH), malondialdehyde (MDA), and total iron detection. Results Forty-nine ferroptosis-related genes were significantly correlated with HCC, 19 of which had prognostic significance. CAPG, SLC7A11 and SQSTM1 were used to construct a novel risk model. The areas under the curves (AUCs) were 0.746 and 0.720 (1 year) in the training and validation groups, respectively. The survival analysis indicated that patients with high risk scores exhibited worse survival in the training and validation groups. The risk score was also identified as an independent prognostic factor of overall survival (OS), which established and validated the predictive abilities of the nomogram. The risk score was also significantly correlated with the expression of immune checkpoint genes. In vitro data showed that CAPG knockdown dramatically suppressed HCC cell proliferation, and the underlying molecular mechanisms might be that the silencing of CAPG reduced the expression of SLC7A11 and promoted ferroptosis. Conclusion The established risk model can be used to predict the prognosis of HCC. At the mechanistic level, CAPG may drive HCC progression by regulating SLC7A11, and ferroptosis activation in HCC patients with high CAPG expression may serve as a potential therapeutic strategy.https://doi.org/10.1007/s12672-023-00677-4Hepatocellular carcinomaFerroptosisPrognosisCAPGSLC7A11 |
| spellingShingle | Qixian Wu Zhenlin Tan Yu Xiong Chengxin Gu Jingdon Zhou Hui Yang Jiyuan Zhou Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma Discover Oncology Hepatocellular carcinoma Ferroptosis Prognosis CAPG SLC7A11 |
| title | Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma |
| title_full | Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma |
| title_fullStr | Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma |
| title_full_unstemmed | Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma |
| title_short | Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma |
| title_sort | comprehensive analysis of ferroptosis related genes for clinical and biological significance in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Ferroptosis Prognosis CAPG SLC7A11 |
| url | https://doi.org/10.1007/s12672-023-00677-4 |
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