Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinoma
IntroductionAnoikis is a distinct form of programmed cell death, differing from classical apoptosis, and its role in malignant tumor progression, particularly in hepatocellular carcinoma (HCC), remains insufficiently understood. This study aims to elucidate the prognostic significance and therapeuti...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1602831/full |
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| author | Xiangyu Zhai Xiangyu Zhai Kecheng Li Hailing Ding Yanmei Wu Xinlu Zhang Hao Zhang Huaxin Zhou Huaxin Zhou Chongzhong Liu Zili Zhang Bin Jin Bin Jin |
| author_facet | Xiangyu Zhai Xiangyu Zhai Kecheng Li Hailing Ding Yanmei Wu Xinlu Zhang Hao Zhang Huaxin Zhou Huaxin Zhou Chongzhong Liu Zili Zhang Bin Jin Bin Jin |
| author_sort | Xiangyu Zhai |
| collection | DOAJ |
| description | IntroductionAnoikis is a distinct form of programmed cell death, differing from classical apoptosis, and its role in malignant tumor progression, particularly in hepatocellular carcinoma (HCC), remains insufficiently understood. This study aims to elucidate the prognostic significance and therapeutic relevance of anoikis-related genes (ARGs) in HCC.MethodsWe systematically analyzed the expression, mutation, and copy number variation profiles of 27 known ARGs in HCC using public datasets. Unsupervised consensus clustering was performed to classify patients into anoikis subtypes. Weighted Gene Co-expression Network Analysis (WGCNA) identified hub gene modules, and LASSO Cox regression was applied to construct a prognostic risk score model. Correlations between the risk model and clinical outcomes, tumor microenvironment (TME) characteristics, and immunotherapy responses were evaluated. Single-cell RNA-seq and pan-cancer analyses were conducted to explore gene expression across cell types and cancer types. Finally, in vitro experiments were performed to validate the biological function of model genes.ResultsTwo distinct anoikis subtypes with differing prognoses and TME features were identified in HCC. A two-gene prognostic model (TTC26 and TPX2) was developed, demonstrating robust performance in predicting patient outcomes. High-risk patients exhibited lower overall survival and distinct immune infiltration profiles. Pan-cancer analysis showed widespread dysregulation of TTC26 and TPX2. In vitro experiments confirmed that TTC26 promotes HCC cell proliferation, migration, and invasion.DiscussionOur findings reveal that anoikis-related molecular classification is closely linked to HCC prognosis and immune landscape. The established prognostic model has potential clinical utility for risk stratification and treatment guidance. TTC26 may serve as a novel biomarker and therapeutic target in HCC. |
| format | Article |
| id | doaj-art-862a219dcb0d44a6ba6d93f5fc5ec617 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-862a219dcb0d44a6ba6d93f5fc5ec6172025-08-20T03:31:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16028311602831Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinomaXiangyu Zhai0Xiangyu Zhai1Kecheng Li2Hailing Ding3Yanmei Wu4Xinlu Zhang5Hao Zhang6Huaxin Zhou7Huaxin Zhou8Chongzhong Liu9Zili Zhang10Bin Jin11Bin Jin12Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, ChinaShandong Province Engineering Research Center for Multidisciplinary Research on Hepatobiliary and Pancreatic Malignant Tumors, Jinan, ChinaMedical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, ChinaSchool of Medicine, Qilu Institute of Technology, Jinan, ChinaInstitute of Basic Medical Sciences, Shandong Maternal and Child Health Hospital, Jinan, ChinaBasic Medical Research Center, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, ChinaShandong Province Engineering Research Center for Multidisciplinary Research on Hepatobiliary and Pancreatic Malignant Tumors, Jinan, ChinaDepartment of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, ChinaShandong Province Engineering Research Center for Multidisciplinary Research on Hepatobiliary and Pancreatic Malignant Tumors, Jinan, ChinaDepartment of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, ChinaDepartment of General Surgery, The Fourth People’s Hospital of Jinan, Jinan, ChinaDepartment of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, ChinaShandong Province Engineering Research Center for Multidisciplinary Research on Hepatobiliary and Pancreatic Malignant Tumors, Jinan, ChinaIntroductionAnoikis is a distinct form of programmed cell death, differing from classical apoptosis, and its role in malignant tumor progression, particularly in hepatocellular carcinoma (HCC), remains insufficiently understood. This study aims to elucidate the prognostic significance and therapeutic relevance of anoikis-related genes (ARGs) in HCC.MethodsWe systematically analyzed the expression, mutation, and copy number variation profiles of 27 known ARGs in HCC using public datasets. Unsupervised consensus clustering was performed to classify patients into anoikis subtypes. Weighted Gene Co-expression Network Analysis (WGCNA) identified hub gene modules, and LASSO Cox regression was applied to construct a prognostic risk score model. Correlations between the risk model and clinical outcomes, tumor microenvironment (TME) characteristics, and immunotherapy responses were evaluated. Single-cell RNA-seq and pan-cancer analyses were conducted to explore gene expression across cell types and cancer types. Finally, in vitro experiments were performed to validate the biological function of model genes.ResultsTwo distinct anoikis subtypes with differing prognoses and TME features were identified in HCC. A two-gene prognostic model (TTC26 and TPX2) was developed, demonstrating robust performance in predicting patient outcomes. High-risk patients exhibited lower overall survival and distinct immune infiltration profiles. Pan-cancer analysis showed widespread dysregulation of TTC26 and TPX2. In vitro experiments confirmed that TTC26 promotes HCC cell proliferation, migration, and invasion.DiscussionOur findings reveal that anoikis-related molecular classification is closely linked to HCC prognosis and immune landscape. The established prognostic model has potential clinical utility for risk stratification and treatment guidance. TTC26 may serve as a novel biomarker and therapeutic target in HCC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1602831/fullanoikishepatocellular carcinomatumor microenvironmentprognostic signatureimmunotherapy response |
| spellingShingle | Xiangyu Zhai Xiangyu Zhai Kecheng Li Hailing Ding Yanmei Wu Xinlu Zhang Hao Zhang Huaxin Zhou Huaxin Zhou Chongzhong Liu Zili Zhang Bin Jin Bin Jin Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinoma Frontiers in Immunology anoikis hepatocellular carcinoma tumor microenvironment prognostic signature immunotherapy response |
| title | Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinoma |
| title_full | Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinoma |
| title_fullStr | Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinoma |
| title_full_unstemmed | Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinoma |
| title_short | Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinoma |
| title_sort | identification of anoikis related subtypes and a risk score prognosis model the association with tme landscapes and therapeutic responses in hepatocellular carcinoma |
| topic | anoikis hepatocellular carcinoma tumor microenvironment prognostic signature immunotherapy response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1602831/full |
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