Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatment
Abstract Hepatocellular carcinoma (HCC) represents a formidable malignancy with a high lethality. Nonetheless, the development of vaccine and the establishment of prognostic models for precise and personalized treatment of HCC still encounter big challenges. Thus, the aim of this study was to develo...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-08-01
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| Series: | Journal of Big Data |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40537-023-00803-7 |
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| author | Zhiyuan Zheng Hantao Yang Yang Shi Feng Zhou Lingxiao Liu Zhiping Yan Xiaolin Wang |
| author_facet | Zhiyuan Zheng Hantao Yang Yang Shi Feng Zhou Lingxiao Liu Zhiping Yan Xiaolin Wang |
| author_sort | Zhiyuan Zheng |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) represents a formidable malignancy with a high lethality. Nonetheless, the development of vaccine and the establishment of prognostic models for precise and personalized treatment of HCC still encounter big challenges. Thus, the aim of this study was to develop HCC vaccines and explore anoikis-based prognostic models based on RNA sequencing data in GEO datasets (GSE10143, GSE76427) and the TCGA-LIHC cohort. Potential HCC antigens were identified using GEPIA2, cBioPortal, and TIMER2. Anoikis-related subtypes and gene clusters were defined by consensus clustering of 566 liver cancer samples based on 28 anoikis regulators, and we further analyzed their relationship with the immune microenvironment of HCC. A predictive model based on anoikis-related long noncoding RNAs (lncRNAs) was developed to accurately predict HCC prognosis. Seven overexpressed genes associated with HCC prognosis and tumor-infiltrating antigen-presenting cells were identified as potential tumor antigens for the development of HCC mRNA vaccines. Two subtypes based on anoikis-related genes (ARGs) and two gene clusters with different characteristics were identified and validated in defined cohorts. The tumor immune microenvironment between the two subtypes showed different cell infiltration and molecular characteristics. Furthermore, a prognostic score based on seven lncRNAs identified by LASSO regression was constructed, with the low-risk group having favorable prognosis, a “hot” immune microenvironment, and better response to immunotherapy. CCNB1, CDK1, DNASE1L3, KPNA2, PRC1, PTTG, and UBE2S were first identified as promising tumor antigens for mRNA vaccine development in HCC. Besides, we innovatively propose anoikis-based molecular subtypes, which not only enable personalized prognostic stratification of HCC patients but also provide a blueprint for identifying optimal candidates for tumor vaccines, enhancing immunotherapeutic strategies. |
| first_indexed | 2024-03-10T17:41:03Z |
| format | Article |
| id | doaj.art-ae72d9a492544813a33fbe984631c341 |
| institution | Directory Open Access Journal |
| issn | 2196-1115 |
| language | English |
| last_indexed | 2024-03-10T17:41:03Z |
| publishDate | 2023-08-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Journal of Big Data |
| spelling | doaj.art-ae72d9a492544813a33fbe984631c3412023-11-20T09:42:37ZengSpringerOpenJournal of Big Data2196-11152023-08-0110113210.1186/s40537-023-00803-7Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatmentZhiyuan Zheng0Hantao Yang1Yang Shi2Feng Zhou3Lingxiao Liu4Zhiping Yan5Xiaolin Wang6Department of Interventional Radiology, Zhongshan Hospital Fudan University and Shanghai Institute of Medical Imaging, Fudan UniversityDepartment of Neurosurgery, Zhongshan Hospital Fudan UniversityFaculty of Medicine, Institute for Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, RWTH Aachen UniversityDepartment of Neurosurgery, Baoji Central HospitalDepartment of Interventional Radiology, Zhongshan Hospital Fudan University and Shanghai Institute of Medical Imaging, Fudan UniversityDepartment of Interventional Radiology, Zhongshan Hospital Fudan University and Shanghai Institute of Medical Imaging, Fudan UniversityDepartment of Interventional Radiology, Zhongshan Hospital Fudan University and Shanghai Institute of Medical Imaging, Fudan UniversityAbstract Hepatocellular carcinoma (HCC) represents a formidable malignancy with a high lethality. Nonetheless, the development of vaccine and the establishment of prognostic models for precise and personalized treatment of HCC still encounter big challenges. Thus, the aim of this study was to develop HCC vaccines and explore anoikis-based prognostic models based on RNA sequencing data in GEO datasets (GSE10143, GSE76427) and the TCGA-LIHC cohort. Potential HCC antigens were identified using GEPIA2, cBioPortal, and TIMER2. Anoikis-related subtypes and gene clusters were defined by consensus clustering of 566 liver cancer samples based on 28 anoikis regulators, and we further analyzed their relationship with the immune microenvironment of HCC. A predictive model based on anoikis-related long noncoding RNAs (lncRNAs) was developed to accurately predict HCC prognosis. Seven overexpressed genes associated with HCC prognosis and tumor-infiltrating antigen-presenting cells were identified as potential tumor antigens for the development of HCC mRNA vaccines. Two subtypes based on anoikis-related genes (ARGs) and two gene clusters with different characteristics were identified and validated in defined cohorts. The tumor immune microenvironment between the two subtypes showed different cell infiltration and molecular characteristics. Furthermore, a prognostic score based on seven lncRNAs identified by LASSO regression was constructed, with the low-risk group having favorable prognosis, a “hot” immune microenvironment, and better response to immunotherapy. CCNB1, CDK1, DNASE1L3, KPNA2, PRC1, PTTG, and UBE2S were first identified as promising tumor antigens for mRNA vaccine development in HCC. Besides, we innovatively propose anoikis-based molecular subtypes, which not only enable personalized prognostic stratification of HCC patients but also provide a blueprint for identifying optimal candidates for tumor vaccines, enhancing immunotherapeutic strategies.https://doi.org/10.1186/s40537-023-00803-7HCCAnoikisPrognosisSubtypeTCGAGEO |
| spellingShingle | Zhiyuan Zheng Hantao Yang Yang Shi Feng Zhou Lingxiao Liu Zhiping Yan Xiaolin Wang Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatment Journal of Big Data HCC Anoikis Prognosis Subtype TCGA GEO |
| title | Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatment |
| title_full | Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatment |
| title_fullStr | Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatment |
| title_full_unstemmed | Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatment |
| title_short | Identification of tumor antigens and anoikis-based molecular subtypes in the hepatocellular carcinoma immune microenvironment: implications for mRNA vaccine development and precision treatment |
| title_sort | identification of tumor antigens and anoikis based molecular subtypes in the hepatocellular carcinoma immune microenvironment implications for mrna vaccine development and precision treatment |
| topic | HCC Anoikis Prognosis Subtype TCGA GEO |
| url | https://doi.org/10.1186/s40537-023-00803-7 |
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