Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma
Abstract Background: Microvascular invasion (MVI) is an independent risk factor of poor prognosis in hepatocellular carcinoma (HCC) and can be used to guide the diagnosis and treatment of HCC. The immune system serves as an integral role in the incidence and progression of HCC. However, the molecula...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-78467-3 |
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| author | Hao Li Lixue Qiao Minyu Kong Haoran Fang Zhiping Yan Ran Guo Wenzhi Guo |
| author_facet | Hao Li Lixue Qiao Minyu Kong Haoran Fang Zhiping Yan Ran Guo Wenzhi Guo |
| author_sort | Hao Li |
| collection | DOAJ |
| description | Abstract Background: Microvascular invasion (MVI) is an independent risk factor of poor prognosis in hepatocellular carcinoma (HCC) and can be used to guide the diagnosis and treatment of HCC. The immune system serves as an integral role in the incidence and progression of HCC. However, the molecular biology correlation between MVI and tumor immunity and the value of combining the two parameters to predict patient prognosis and HCC response to treatment remain to be evaluated. Results: In this study, we used univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to establish the MVI and immune-related gene index (MIRGPI) including eight genes. We demonstrated that the MIRGPI was an independent risk factor in predicting the prognosis of HCC. Subsequently, our research established a nomogram model combining pathologic characteristics and verified its good clinical application value. In addition, our study found that the TP53 gene had a higher mutation frequency and a lower degree of immune infiltration in the high-risk group. The low-risk group had higher sensitivity to immunotherapy, sorafenib, and TACE treatment, and the high-risk group had higher sensitivity to common chemotherapeutic agents. Finally, SEMA3C was found to facilitate the proliferation, migration and invasive ability of HCC by in vitro and in vivo experiments, and its mechanism may be associated with the activation of the NF-Κb/EMT signaling pathway. Conclusions: In summary, the MIRGPI signature we developed is a reliable marker for the prediction of prognosis and treatment response, and is important for the prognostic assessment and individualized treatment of HCC. |
| format | Article |
| id | doaj-art-2bd879accea346fb9182123b899406c9 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-2bd879accea346fb9182123b899406c92025-08-20T02:49:58ZengNature PortfolioScientific Reports2045-23222024-11-0114111910.1038/s41598-024-78467-3Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinomaHao Li0Lixue Qiao1Minyu Kong2Haoran Fang3Zhiping Yan4Ran Guo5Wenzhi Guo6Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou UniversityThyroid Surgery Department, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background: Microvascular invasion (MVI) is an independent risk factor of poor prognosis in hepatocellular carcinoma (HCC) and can be used to guide the diagnosis and treatment of HCC. The immune system serves as an integral role in the incidence and progression of HCC. However, the molecular biology correlation between MVI and tumor immunity and the value of combining the two parameters to predict patient prognosis and HCC response to treatment remain to be evaluated. Results: In this study, we used univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to establish the MVI and immune-related gene index (MIRGPI) including eight genes. We demonstrated that the MIRGPI was an independent risk factor in predicting the prognosis of HCC. Subsequently, our research established a nomogram model combining pathologic characteristics and verified its good clinical application value. In addition, our study found that the TP53 gene had a higher mutation frequency and a lower degree of immune infiltration in the high-risk group. The low-risk group had higher sensitivity to immunotherapy, sorafenib, and TACE treatment, and the high-risk group had higher sensitivity to common chemotherapeutic agents. Finally, SEMA3C was found to facilitate the proliferation, migration and invasive ability of HCC by in vitro and in vivo experiments, and its mechanism may be associated with the activation of the NF-Κb/EMT signaling pathway. Conclusions: In summary, the MIRGPI signature we developed is a reliable marker for the prediction of prognosis and treatment response, and is important for the prognostic assessment and individualized treatment of HCC.https://doi.org/10.1038/s41598-024-78467-3Hepatocellular carcinomaMVIImmune-related genesPrognostic biomarkerSEMA3C |
| spellingShingle | Hao Li Lixue Qiao Minyu Kong Haoran Fang Zhiping Yan Ran Guo Wenzhi Guo Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma Scientific Reports Hepatocellular carcinoma MVI Immune-related genes Prognostic biomarker SEMA3C |
| title | Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma |
| title_full | Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma |
| title_fullStr | Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma |
| title_full_unstemmed | Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma |
| title_short | Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma |
| title_sort | construction and validation of a prognostic signature based on microvascular invasion and immune related genes in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma MVI Immune-related genes Prognostic biomarker SEMA3C |
| url | https://doi.org/10.1038/s41598-024-78467-3 |
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