{"title":"胃癌二硫中毒相关预后特征及免疫微环境特征的综合分析与实验验证。","authors":"Huangjie Zhang, Jinguo Hu, Yuanqiang Li, Yanyang Liu, Huize Shen, Zeng Wang, Qinglin Li","doi":"10.1007/s00262-024-03883-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide. As a novel form of programmed cell death, disulfidptosis is characterized by excessive cysteine accumulation, disulfide stress and actin destruction. There is evidence that targeting disulfidptosis is a promising anticancer strategy. Further improvement of GC risk stratification based on disulfidptosis has positive clinical significance.</p><p><strong>Methods: </strong>We analyzed the expression levels of disulfidptosis-associated genes (DPAGs) in normal and GC tissues and characterized the molecular subtypes of GC patients. Based on the characteristics of DPAG subtypes, differentially expressed prognosis-related genes were selected by LASSO-univariate Cox analysis and multivariate Cox analysis analyzed to establish a prognostic model. Using single-cell sequencing analysis reveals the cell subpopulation for GC. The function of the selected target in GC was verified by in vitro experimental means, including siRNA, qRT-PCR, Western blot, CCK-8, and Transwell assay.</p><p><strong>Results: </strong>DPAG score was verified to be an independent prognostic factor of GC and was significantly associated with poor prognosis of gastric cancer. Subsequent studies on subgroup immunoinfiltration characteristics, drug sensitivity analysis, immunotherapy response and somatic mutation characteristics of DPAG score comprehensively confirmed the potential guiding significance of DPAG score for individualized treatment of gastric cancer patients. Single-cell sequencing analysis revealed the expression characteristics of DPAG-related prognostic signatures across cell subpopulations. In vitro experiments showed APC11, as one of the selected DPAGs, was highly expressed in gastric cancer, and knockdown of APC11 could significantly inhibit the proliferation and migration of GC cells, demonstrating the reliability of bioinformatics results.</p><p><strong>Conclusion: </strong>The results of this study provide a new perspective for exploring the role of disulfidptosis in the occurrence and development of GC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"116"},"PeriodicalIF":4.6000,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861452/pdf/","citationCount":"0","resultStr":"{\"title\":\"Comprehensive analysis and experimental validation of disulfidptosis-associated prognostic signature and immune microenvironment characterization of gastric cancer.\",\"authors\":\"Huangjie Zhang, Jinguo Hu, Yuanqiang Li, Yanyang Liu, Huize Shen, Zeng Wang, Qinglin Li\",\"doi\":\"10.1007/s00262-024-03883-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide. As a novel form of programmed cell death, disulfidptosis is characterized by excessive cysteine accumulation, disulfide stress and actin destruction. There is evidence that targeting disulfidptosis is a promising anticancer strategy. Further improvement of GC risk stratification based on disulfidptosis has positive clinical significance.</p><p><strong>Methods: </strong>We analyzed the expression levels of disulfidptosis-associated genes (DPAGs) in normal and GC tissues and characterized the molecular subtypes of GC patients. Based on the characteristics of DPAG subtypes, differentially expressed prognosis-related genes were selected by LASSO-univariate Cox analysis and multivariate Cox analysis analyzed to establish a prognostic model. Using single-cell sequencing analysis reveals the cell subpopulation for GC. The function of the selected target in GC was verified by in vitro experimental means, including siRNA, qRT-PCR, Western blot, CCK-8, and Transwell assay.</p><p><strong>Results: </strong>DPAG score was verified to be an independent prognostic factor of GC and was significantly associated with poor prognosis of gastric cancer. Subsequent studies on subgroup immunoinfiltration characteristics, drug sensitivity analysis, immunotherapy response and somatic mutation characteristics of DPAG score comprehensively confirmed the potential guiding significance of DPAG score for individualized treatment of gastric cancer patients. Single-cell sequencing analysis revealed the expression characteristics of DPAG-related prognostic signatures across cell subpopulations. In vitro experiments showed APC11, as one of the selected DPAGs, was highly expressed in gastric cancer, and knockdown of APC11 could significantly inhibit the proliferation and migration of GC cells, demonstrating the reliability of bioinformatics results.</p><p><strong>Conclusion: </strong>The results of this study provide a new perspective for exploring the role of disulfidptosis in the occurrence and development of GC.</p>\",\"PeriodicalId\":9595,\"journal\":{\"name\":\"Cancer Immunology, Immunotherapy\",\"volume\":\"74 4\",\"pages\":\"116\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-02-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861452/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Immunology, Immunotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00262-024-03883-3\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Immunology, Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-024-03883-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Comprehensive analysis and experimental validation of disulfidptosis-associated prognostic signature and immune microenvironment characterization of gastric cancer.
Background: Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide. As a novel form of programmed cell death, disulfidptosis is characterized by excessive cysteine accumulation, disulfide stress and actin destruction. There is evidence that targeting disulfidptosis is a promising anticancer strategy. Further improvement of GC risk stratification based on disulfidptosis has positive clinical significance.
Methods: We analyzed the expression levels of disulfidptosis-associated genes (DPAGs) in normal and GC tissues and characterized the molecular subtypes of GC patients. Based on the characteristics of DPAG subtypes, differentially expressed prognosis-related genes were selected by LASSO-univariate Cox analysis and multivariate Cox analysis analyzed to establish a prognostic model. Using single-cell sequencing analysis reveals the cell subpopulation for GC. The function of the selected target in GC was verified by in vitro experimental means, including siRNA, qRT-PCR, Western blot, CCK-8, and Transwell assay.
Results: DPAG score was verified to be an independent prognostic factor of GC and was significantly associated with poor prognosis of gastric cancer. Subsequent studies on subgroup immunoinfiltration characteristics, drug sensitivity analysis, immunotherapy response and somatic mutation characteristics of DPAG score comprehensively confirmed the potential guiding significance of DPAG score for individualized treatment of gastric cancer patients. Single-cell sequencing analysis revealed the expression characteristics of DPAG-related prognostic signatures across cell subpopulations. In vitro experiments showed APC11, as one of the selected DPAGs, was highly expressed in gastric cancer, and knockdown of APC11 could significantly inhibit the proliferation and migration of GC cells, demonstrating the reliability of bioinformatics results.
Conclusion: The results of this study provide a new perspective for exploring the role of disulfidptosis in the occurrence and development of GC.
期刊介绍：
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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