An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancers
BackgroundGastrointestinal (GI) cancers have high incidence rates and mortality rates. Anoikis is a special type of cell apoptosis, and anoikis resistance has been reported to be associated with tumor malignancy. We aimed to explore the roles of anoikis-related genes (ARGs) in the GI cancer prognosi...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1477913/full |
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| author | Ruyi Liu Ruyi Liu Ruyi Liu Ruyi Liu Ruyi Liu Yuchen Liu Yuchen Liu Yuchen Liu Yuchen Liu Yuchen Liu Weicheng Huang Weicheng Huang Weicheng Huang Weicheng Huang Weicheng Huang Pengxiang Chen Pengxiang Chen Pengxiang Chen Pengxiang Chen Pengxiang Chen Yufeng Cheng Yufeng Cheng Yufeng Cheng Yufeng Cheng Yufeng Cheng |
| author_facet | Ruyi Liu Ruyi Liu Ruyi Liu Ruyi Liu Ruyi Liu Yuchen Liu Yuchen Liu Yuchen Liu Yuchen Liu Yuchen Liu Weicheng Huang Weicheng Huang Weicheng Huang Weicheng Huang Weicheng Huang Pengxiang Chen Pengxiang Chen Pengxiang Chen Pengxiang Chen Pengxiang Chen Yufeng Cheng Yufeng Cheng Yufeng Cheng Yufeng Cheng Yufeng Cheng |
| author_sort | Ruyi Liu |
| collection | DOAJ |
| description | BackgroundGastrointestinal (GI) cancers have high incidence rates and mortality rates. Anoikis is a special type of cell apoptosis, and anoikis resistance has been reported to be associated with tumor malignancy. We aimed to explore the roles of anoikis-related genes (ARGs) in the GI cancer prognosis.MethodsWe extracted RNA sequencing and clinical data from The Cancer Genome Atlas and Gene Expression Omnibu databases for patients with esophageal cancer, gastric cancer, colon cancer and rectal cancer and identified ARGs from GeneCards and Harmonizome. Anoikis-related patterns were identified via unsupervised clustering analysis. We constructed a prognostic signature (Anoscore) based on prognostic ARGs through univariate, LASSO, and multivariate Cox regression analyses. The model was validated and evaluated using Kaplan–Meier analysis, receiver operating characteristic curves, univariate Cox regression analysis, multivariate Cox regression analysis, column charts, and calibration curves. We also performed a single-cell sequencing analysis of candidate genes via TISCH2. A correlation analysis between the Anoscore, the tumor microenvironment and drug sensitivity was conducted in GI cancers. The expression and function of some candidate genes were validated in vitro.ResultsIn terms of prognostic ARGs, two anoikis-related patterns, ARG clusters A and B, were identified. ARG cluster B had a worse prognosis than did ARG cluster A. Subsequently, the Anoscore was developed as an independent prognostic factor. It demonstrated the robust predictive capability for the prognosis of patients with GI cancers. Notably, patients with high Anoscores exhibited poor outcomes. In addition, we established a nomogram (Ano-nomogram) based on the Anoscore and clinicopathological factors of patients to predict the 3-year and 5-year survival probabilities. Moreover, patients with high Anoscores had higher levels of immune cell infiltration and higher immune checkpoint expression. The drug sensitivity analysis revealed that patients with high or low Anoscores were sensitive to different chemotherapies and targeted drugs. S100A11 and TLR3, representative candidate genes, exhibited different expression patterns and biological functions.ConclusionThis study highlighted the significant potential of the Anoscore in predicting prognosis and guiding the selection of personalized therapeutic regimens for patients with GI cancers. |
| format | Article |
| id | doaj-art-e9bf1ab916bc43988a15694272aa1e06 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-e9bf1ab916bc43988a15694272aa1e062025-02-06T07:09:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14779131477913An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancersRuyi Liu0Ruyi Liu1Ruyi Liu2Ruyi Liu3Ruyi Liu4Yuchen Liu5Yuchen Liu6Yuchen Liu7Yuchen Liu8Yuchen Liu9Weicheng Huang10Weicheng Huang11Weicheng Huang12Weicheng Huang13Weicheng Huang14Pengxiang Chen15Pengxiang Chen16Pengxiang Chen17Pengxiang Chen18Pengxiang Chen19Yufeng Cheng20Yufeng Cheng21Yufeng Cheng22Yufeng Cheng23Yufeng Cheng24Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Malignant Tumor Precision Treatment, Jinan, ChinaShandong Provincial Engineering Research Center for Tumor Precision Treatment, Jinan, ChinaCancer Institute of Shandong University, Jinan, ChinaNeutron Medical Center, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Malignant Tumor Precision Treatment, Jinan, ChinaShandong Provincial Engineering Research Center for Tumor Precision Treatment, Jinan, ChinaCancer Institute of Shandong University, Jinan, ChinaNeutron Medical Center, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Malignant Tumor Precision Treatment, Jinan, ChinaShandong Provincial Engineering Research Center for Tumor Precision Treatment, Jinan, ChinaCancer Institute of Shandong University, Jinan, ChinaNeutron Medical Center, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Malignant Tumor Precision Treatment, Jinan, ChinaShandong Provincial Engineering Research Center for Tumor Precision Treatment, Jinan, ChinaCancer Institute of Shandong University, Jinan, ChinaNeutron Medical Center, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Malignant Tumor Precision Treatment, Jinan, ChinaShandong Provincial Engineering Research Center for Tumor Precision Treatment, Jinan, ChinaCancer Institute of Shandong University, Jinan, ChinaNeutron Medical Center, Qilu Hospital of Shandong University, Jinan, ChinaBackgroundGastrointestinal (GI) cancers have high incidence rates and mortality rates. Anoikis is a special type of cell apoptosis, and anoikis resistance has been reported to be associated with tumor malignancy. We aimed to explore the roles of anoikis-related genes (ARGs) in the GI cancer prognosis.MethodsWe extracted RNA sequencing and clinical data from The Cancer Genome Atlas and Gene Expression Omnibu databases for patients with esophageal cancer, gastric cancer, colon cancer and rectal cancer and identified ARGs from GeneCards and Harmonizome. Anoikis-related patterns were identified via unsupervised clustering analysis. We constructed a prognostic signature (Anoscore) based on prognostic ARGs through univariate, LASSO, and multivariate Cox regression analyses. The model was validated and evaluated using Kaplan–Meier analysis, receiver operating characteristic curves, univariate Cox regression analysis, multivariate Cox regression analysis, column charts, and calibration curves. We also performed a single-cell sequencing analysis of candidate genes via TISCH2. A correlation analysis between the Anoscore, the tumor microenvironment and drug sensitivity was conducted in GI cancers. The expression and function of some candidate genes were validated in vitro.ResultsIn terms of prognostic ARGs, two anoikis-related patterns, ARG clusters A and B, were identified. ARG cluster B had a worse prognosis than did ARG cluster A. Subsequently, the Anoscore was developed as an independent prognostic factor. It demonstrated the robust predictive capability for the prognosis of patients with GI cancers. Notably, patients with high Anoscores exhibited poor outcomes. In addition, we established a nomogram (Ano-nomogram) based on the Anoscore and clinicopathological factors of patients to predict the 3-year and 5-year survival probabilities. Moreover, patients with high Anoscores had higher levels of immune cell infiltration and higher immune checkpoint expression. The drug sensitivity analysis revealed that patients with high or low Anoscores were sensitive to different chemotherapies and targeted drugs. S100A11 and TLR3, representative candidate genes, exhibited different expression patterns and biological functions.ConclusionThis study highlighted the significant potential of the Anoscore in predicting prognosis and guiding the selection of personalized therapeutic regimens for patients with GI cancers.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1477913/fullgastrointestinal cancersanoikisprognostic predictionimmunotherapytumor immune microenvironment |
| spellingShingle | Ruyi Liu Ruyi Liu Ruyi Liu Ruyi Liu Ruyi Liu Yuchen Liu Yuchen Liu Yuchen Liu Yuchen Liu Yuchen Liu Weicheng Huang Weicheng Huang Weicheng Huang Weicheng Huang Weicheng Huang Pengxiang Chen Pengxiang Chen Pengxiang Chen Pengxiang Chen Pengxiang Chen Yufeng Cheng Yufeng Cheng Yufeng Cheng Yufeng Cheng Yufeng Cheng An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancers Frontiers in Immunology gastrointestinal cancers anoikis prognostic prediction immunotherapy tumor immune microenvironment |
| title | An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancers |
| title_full | An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancers |
| title_fullStr | An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancers |
| title_full_unstemmed | An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancers |
| title_short | An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancers |
| title_sort | anoikis related signature predicts prognosis and immunotherapy response in gastrointestinal cancers |
| topic | gastrointestinal cancers anoikis prognostic prediction immunotherapy tumor immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1477913/full |
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