Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma
Abstract Stomach adenocarcinoma (STAD) is the most prevalent gastrointestinal malignancy and seriously threatens the life of the global population. Anoikis, a process of programmed cell death that occurs when cells detach from the extracellular matrix, is closely associated with tumor invasion and m...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88882-9 |
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| author | Ziyi Zhou Lanlan Yang Yuan Fang Rongzhong Xu Xi Wang Yuli Wang Zhihong Fang |
| author_facet | Ziyi Zhou Lanlan Yang Yuan Fang Rongzhong Xu Xi Wang Yuli Wang Zhihong Fang |
| author_sort | Ziyi Zhou |
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| description | Abstract Stomach adenocarcinoma (STAD) is the most prevalent gastrointestinal malignancy and seriously threatens the life of the global population. Anoikis, a process of programmed cell death that occurs when cells detach from the extracellular matrix, is closely associated with tumor invasion and metastasis. In this study, we used the TCGA-STAD database to identify the expression patterns and prognostic relevance of anoikis-related genes (ARGs) in STAD. Functional enrichment analysis was used to explore the potential pathway. LASSO and Cox regression were used to construct anoikis-related prognostic signature. The anoikis risk score (ARS) incorporated 7 genes and stratified patients into highand low-risk subgroups by median value splitting. In addition, external validation was performed based on GSE66229, GSE15459, and GSE84437 cohorts. Nomograms were created based on risk characteristics in combination with clinical variants and the performance of the model was validated with time-dependent AUC, calibration curves, and decision curve analysis (DCA). The prognostic signature indicated that the low-risk subgroup had better outcomes and significant correlations with tumor microenvironment, immune landscape, immunotherapy response, and drug sensitivity. In addition, single-cell analysis displayed the cell types, the subcellular localization of prognostic genes, and the cellular interaction to reveal the potential molecular communication mechanism of anoikis resistance. Finally, in vitro experiments confirmed the critical role of CRABP2 in STAD. The results indicated that CRABP2 knockdown inhibited gastric cancer cell proliferation, migration and invasion, and promoted apoptosis. In summary, ARS can serve as a biomarker for predicting survival outcomes in STAD patients, providing new tools for personalized treatment decisions for STAD patients. |
| format | Article |
| id | doaj-art-1e051bac88c04d7c9363ed89370294e6 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-1e051bac88c04d7c9363ed89370294e62025-02-09T12:35:11ZengNature PortfolioScientific Reports2045-23222025-02-0115112010.1038/s41598-025-88882-9Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinomaZiyi Zhou0Lanlan Yang1Yuan Fang2Rongzhong Xu3Xi Wang4Yuli Wang5Zhihong Fang6Clinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineAbstract Stomach adenocarcinoma (STAD) is the most prevalent gastrointestinal malignancy and seriously threatens the life of the global population. Anoikis, a process of programmed cell death that occurs when cells detach from the extracellular matrix, is closely associated with tumor invasion and metastasis. In this study, we used the TCGA-STAD database to identify the expression patterns and prognostic relevance of anoikis-related genes (ARGs) in STAD. Functional enrichment analysis was used to explore the potential pathway. LASSO and Cox regression were used to construct anoikis-related prognostic signature. The anoikis risk score (ARS) incorporated 7 genes and stratified patients into highand low-risk subgroups by median value splitting. In addition, external validation was performed based on GSE66229, GSE15459, and GSE84437 cohorts. Nomograms were created based on risk characteristics in combination with clinical variants and the performance of the model was validated with time-dependent AUC, calibration curves, and decision curve analysis (DCA). The prognostic signature indicated that the low-risk subgroup had better outcomes and significant correlations with tumor microenvironment, immune landscape, immunotherapy response, and drug sensitivity. In addition, single-cell analysis displayed the cell types, the subcellular localization of prognostic genes, and the cellular interaction to reveal the potential molecular communication mechanism of anoikis resistance. Finally, in vitro experiments confirmed the critical role of CRABP2 in STAD. The results indicated that CRABP2 knockdown inhibited gastric cancer cell proliferation, migration and invasion, and promoted apoptosis. In summary, ARS can serve as a biomarker for predicting survival outcomes in STAD patients, providing new tools for personalized treatment decisions for STAD patients.https://doi.org/10.1038/s41598-025-88882-9BioinformaticsStomach adenocarcinomaAnoikisTumor microenvironmentImmune landscape |
| spellingShingle | Ziyi Zhou Lanlan Yang Yuan Fang Rongzhong Xu Xi Wang Yuli Wang Zhihong Fang Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma Scientific Reports Bioinformatics Stomach adenocarcinoma Anoikis Tumor microenvironment Immune landscape |
| title | Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma |
| title_full | Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma |
| title_fullStr | Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma |
| title_full_unstemmed | Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma |
| title_short | Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma |
| title_sort | integrative analysis of anoikis related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma |
| topic | Bioinformatics Stomach adenocarcinoma Anoikis Tumor microenvironment Immune landscape |
| url | https://doi.org/10.1038/s41598-025-88882-9 |
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