Zicheng Shao, Mostafa A Abdel-Maksoud, Ibrahim A Saleh, Jehad S Al-Hawadi, Naser Zomot, Saeedah Musaed Almutairi, Jie Chen
{"title":"胰腺腺癌中成纤维细胞生长因子结合蛋白1(FGFBP1)的多组学综合分析及其预后意义","authors":"Zicheng Shao, Mostafa A Abdel-Maksoud, Ibrahim A Saleh, Jehad S Al-Hawadi, Naser Zomot, Saeedah Musaed Almutairi, Jie Chen","doi":"10.62347/NCRX9798","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer with poor prognosis and limited therapeutic options. Identifying molecular markers and understanding their role in PAAD pathogenesis is crucial for developing targeted therapies. This study integrates bioinformatics and molecular experiments to investigate the diagnostic, prognostic, and therapeutic significance of FGFBP1 in PAAD.</p><p><strong>Methods: </strong>UALCAN, TNMplot, OncoDB, GEPIA2, HPA, GSCA, KM Plotter, TISIDB, TISCH2, CancerSEA, STRING, DAVID, cell culture, RT-qPCR analysis, western blot analysis, colony formation, cell proliferation, and wound healing assays.</p><p><strong>Results: </strong>Expression analyses revealed a significantly elevated FGFBP1 levels in PAAD tissues compared to normal samples. Promoter methylation analysis indicated lower methylation levels in PAAD, inversely correlated with FGFBP1 expression, suggesting epigenetic regulation. Genetic alteration analysis showed that FGFBP1 is not significantly affected by single nucleotide variants, but copy number variations are present without impacting mRNA expression. Survival analysis using KM plotter demonstrated that high FGFBP1 expression is associated with poor overall and disease-free survival. A Cox regression-based prognostic model confirmed the negative impact of elevated FGFBP1 on patient outcomes. Correlation analysis with immune-related factors indicated that FGFBP1 may contribute to an immunosuppressive tumor microenvironment, affecting immune cell infiltration and function. Single-cell analysis highlighted FGFBP1 expression in malignant, endothelial, and fibroblast cells within the tumor microenvironment. Gene enrichment analysis revealed FGFBP1's involvement in various biological processes and pathways related to cancer progression. Experimental validation using RT-qPCR confirmed high FGFBP1 expression in PAAD cell lines. FGFBP1 knockdown in HEK293T cells significantly reduced cell proliferation, colony formation, and migration.</p><p><strong>Conclusion: </strong>These findings suggest that FGFBP1 plays a critical role in PAAD pathogenesis and could serve as a potential therapeutic target for improving patient outcomes.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384405/pdf/","citationCount":"0","resultStr":"{\"title\":\"Comprehensive multi-omics analysis and prognostic significance of fibroblast growth factor binding protein 1 (FGFBP1) in pancreatic adenocarcinoma.\",\"authors\":\"Zicheng Shao, Mostafa A Abdel-Maksoud, Ibrahim A Saleh, Jehad S Al-Hawadi, Naser Zomot, Saeedah Musaed Almutairi, Jie Chen\",\"doi\":\"10.62347/NCRX9798\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer with poor prognosis and limited therapeutic options. Identifying molecular markers and understanding their role in PAAD pathogenesis is crucial for developing targeted therapies. This study integrates bioinformatics and molecular experiments to investigate the diagnostic, prognostic, and therapeutic significance of FGFBP1 in PAAD.</p><p><strong>Methods: </strong>UALCAN, TNMplot, OncoDB, GEPIA2, HPA, GSCA, KM Plotter, TISIDB, TISCH2, CancerSEA, STRING, DAVID, cell culture, RT-qPCR analysis, western blot analysis, colony formation, cell proliferation, and wound healing assays.</p><p><strong>Results: </strong>Expression analyses revealed a significantly elevated FGFBP1 levels in PAAD tissues compared to normal samples. Promoter methylation analysis indicated lower methylation levels in PAAD, inversely correlated with FGFBP1 expression, suggesting epigenetic regulation. Genetic alteration analysis showed that FGFBP1 is not significantly affected by single nucleotide variants, but copy number variations are present without impacting mRNA expression. Survival analysis using KM plotter demonstrated that high FGFBP1 expression is associated with poor overall and disease-free survival. A Cox regression-based prognostic model confirmed the negative impact of elevated FGFBP1 on patient outcomes. Correlation analysis with immune-related factors indicated that FGFBP1 may contribute to an immunosuppressive tumor microenvironment, affecting immune cell infiltration and function. Single-cell analysis highlighted FGFBP1 expression in malignant, endothelial, and fibroblast cells within the tumor microenvironment. Gene enrichment analysis revealed FGFBP1's involvement in various biological processes and pathways related to cancer progression. Experimental validation using RT-qPCR confirmed high FGFBP1 expression in PAAD cell lines. FGFBP1 knockdown in HEK293T cells significantly reduced cell proliferation, colony formation, and migration.</p><p><strong>Conclusion: </strong>These findings suggest that FGFBP1 plays a critical role in PAAD pathogenesis and could serve as a potential therapeutic target for improving patient outcomes.</p>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384405/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.62347/NCRX9798\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/NCRX9798","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Comprehensive multi-omics analysis and prognostic significance of fibroblast growth factor binding protein 1 (FGFBP1) in pancreatic adenocarcinoma.
Background: Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer with poor prognosis and limited therapeutic options. Identifying molecular markers and understanding their role in PAAD pathogenesis is crucial for developing targeted therapies. This study integrates bioinformatics and molecular experiments to investigate the diagnostic, prognostic, and therapeutic significance of FGFBP1 in PAAD.
Methods: UALCAN, TNMplot, OncoDB, GEPIA2, HPA, GSCA, KM Plotter, TISIDB, TISCH2, CancerSEA, STRING, DAVID, cell culture, RT-qPCR analysis, western blot analysis, colony formation, cell proliferation, and wound healing assays.
Results: Expression analyses revealed a significantly elevated FGFBP1 levels in PAAD tissues compared to normal samples. Promoter methylation analysis indicated lower methylation levels in PAAD, inversely correlated with FGFBP1 expression, suggesting epigenetic regulation. Genetic alteration analysis showed that FGFBP1 is not significantly affected by single nucleotide variants, but copy number variations are present without impacting mRNA expression. Survival analysis using KM plotter demonstrated that high FGFBP1 expression is associated with poor overall and disease-free survival. A Cox regression-based prognostic model confirmed the negative impact of elevated FGFBP1 on patient outcomes. Correlation analysis with immune-related factors indicated that FGFBP1 may contribute to an immunosuppressive tumor microenvironment, affecting immune cell infiltration and function. Single-cell analysis highlighted FGFBP1 expression in malignant, endothelial, and fibroblast cells within the tumor microenvironment. Gene enrichment analysis revealed FGFBP1's involvement in various biological processes and pathways related to cancer progression. Experimental validation using RT-qPCR confirmed high FGFBP1 expression in PAAD cell lines. FGFBP1 knockdown in HEK293T cells significantly reduced cell proliferation, colony formation, and migration.
Conclusion: These findings suggest that FGFBP1 plays a critical role in PAAD pathogenesis and could serve as a potential therapeutic target for improving patient outcomes.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.