{"title":"胃癌嗜酸症相关基因的鉴定：生物信息学和实验验证","authors":"Chao Song, Wenbo Liu, Xiaoyu Wang, Xin Liu, Zhiran Yang, Yingying Wang, Qun Zhao, Yong Li, Mingming Zhang, Bibo Tan","doi":"10.1002/cam4.70907","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>Distant metastasis is the main reason for the poor prognosis of gastric cancer, and anoikis refers to the cell death caused when cells detach from the extracellular matrix or adhere in incorrect locations, playing an important role in the distant metastasis of gastric cancer.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Download the TCGA-STAD dataset and the anoikis gene set, and filter out the differentially expressed anoikis genes. Perform consensus clustering of gastric cancer samples, and conduct Weighted Gene Correlation Network Analysis (WGCNA), enrichment analysis, and immune infiltration analysis for the expression characteristics of each subtype, while also filtering the genes with differential expression between subtypes. Additionally, through COX survival analysis, identify anoikis genes related to gastric cancer prognosis and establish a nomogram. Finally, validate the differentially expressed gene CYP1B1 in vivo and in vitro through clinical samples, cell culture, and the establishment of an anoikis model.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Three subtypes of gastric cancer with anoikis genes were identified, each exhibiting different expression characteristics, biological pathways, and immune cell infiltration. The abundance of activated NK cells, memory B cells, and M2 macrophages showed significant differences among the three subtypes. We screened four differentially expressed gene sets and five genes (CYP1B1, EQTN, NRXN2, TBC1D3E, TCEAL5) among the three subtypes. Through survival analysis, we identified 33 independent prognostic genes and constructed a nomogram, with calibration curves indicating good consistency. Finally, we selected CYP1B1 for experimental validation, and in vivo and in vitro experiments demonstrated that CYP1B1 is highly expressed in gastric cancer, participates in the resistance to cell death in gastric cancer cells, and promotes the invasion, migration, and tumor progression of gastric cancer cells.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The expression patterns of subtypes based on differentially expressed genes related to anoikis in gastric cancer vary, providing theoretical support for the future of personalized treatment for gastric cancer.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 8","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70907","citationCount":"0","resultStr":"{\"title\":\"Identification of Anoikis-Related Genes in Gastric Cancer: Bioinformatics and Experimental Validation\",\"authors\":\"Chao Song, Wenbo Liu, Xiaoyu Wang, Xin Liu, Zhiran Yang, Yingying Wang, Qun Zhao, Yong Li, Mingming Zhang, Bibo Tan\",\"doi\":\"10.1002/cam4.70907\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>Distant metastasis is the main reason for the poor prognosis of gastric cancer, and anoikis refers to the cell death caused when cells detach from the extracellular matrix or adhere in incorrect locations, playing an important role in the distant metastasis of gastric cancer.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Download the TCGA-STAD dataset and the anoikis gene set, and filter out the differentially expressed anoikis genes. Perform consensus clustering of gastric cancer samples, and conduct Weighted Gene Correlation Network Analysis (WGCNA), enrichment analysis, and immune infiltration analysis for the expression characteristics of each subtype, while also filtering the genes with differential expression between subtypes. Additionally, through COX survival analysis, identify anoikis genes related to gastric cancer prognosis and establish a nomogram. Finally, validate the differentially expressed gene CYP1B1 in vivo and in vitro through clinical samples, cell culture, and the establishment of an anoikis model.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Three subtypes of gastric cancer with anoikis genes were identified, each exhibiting different expression characteristics, biological pathways, and immune cell infiltration. The abundance of activated NK cells, memory B cells, and M2 macrophages showed significant differences among the three subtypes. We screened four differentially expressed gene sets and five genes (CYP1B1, EQTN, NRXN2, TBC1D3E, TCEAL5) among the three subtypes. Through survival analysis, we identified 33 independent prognostic genes and constructed a nomogram, with calibration curves indicating good consistency. Finally, we selected CYP1B1 for experimental validation, and in vivo and in vitro experiments demonstrated that CYP1B1 is highly expressed in gastric cancer, participates in the resistance to cell death in gastric cancer cells, and promotes the invasion, migration, and tumor progression of gastric cancer cells.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>The expression patterns of subtypes based on differentially expressed genes related to anoikis in gastric cancer vary, providing theoretical support for the future of personalized treatment for gastric cancer.</p>\\n </section>\\n </div>\",\"PeriodicalId\":139,\"journal\":{\"name\":\"Cancer Medicine\",\"volume\":\"14 8\",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-04-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70907\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70907\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70907","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Identification of Anoikis-Related Genes in Gastric Cancer: Bioinformatics and Experimental Validation
Introduction
Distant metastasis is the main reason for the poor prognosis of gastric cancer, and anoikis refers to the cell death caused when cells detach from the extracellular matrix or adhere in incorrect locations, playing an important role in the distant metastasis of gastric cancer.
Methods
Download the TCGA-STAD dataset and the anoikis gene set, and filter out the differentially expressed anoikis genes. Perform consensus clustering of gastric cancer samples, and conduct Weighted Gene Correlation Network Analysis (WGCNA), enrichment analysis, and immune infiltration analysis for the expression characteristics of each subtype, while also filtering the genes with differential expression between subtypes. Additionally, through COX survival analysis, identify anoikis genes related to gastric cancer prognosis and establish a nomogram. Finally, validate the differentially expressed gene CYP1B1 in vivo and in vitro through clinical samples, cell culture, and the establishment of an anoikis model.
Results
Three subtypes of gastric cancer with anoikis genes were identified, each exhibiting different expression characteristics, biological pathways, and immune cell infiltration. The abundance of activated NK cells, memory B cells, and M2 macrophages showed significant differences among the three subtypes. We screened four differentially expressed gene sets and five genes (CYP1B1, EQTN, NRXN2, TBC1D3E, TCEAL5) among the three subtypes. Through survival analysis, we identified 33 independent prognostic genes and constructed a nomogram, with calibration curves indicating good consistency. Finally, we selected CYP1B1 for experimental validation, and in vivo and in vitro experiments demonstrated that CYP1B1 is highly expressed in gastric cancer, participates in the resistance to cell death in gastric cancer cells, and promotes the invasion, migration, and tumor progression of gastric cancer cells.
Conclusion
The expression patterns of subtypes based on differentially expressed genes related to anoikis in gastric cancer vary, providing theoretical support for the future of personalized treatment for gastric cancer.
期刊介绍：
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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