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

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-08-15 eCollection Date: 2024-01-01 DOI:10.62347/NCRX9798
Zicheng Shao, Mostafa A Abdel-Maksoud, Ibrahim A Saleh, Jehad S Al-Hawadi, Naser Zomot, Saeedah Musaed Almutairi, Jie Chen
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引用次数: 0

摘要

背景:胰腺腺癌(PAAD)是一种侵袭性极强的癌症,预后不良,治疗方案有限。确定分子标记物并了解它们在 PAAD 发病机制中的作用对于开发靶向疗法至关重要。本研究整合了生物信息学和分子实验,研究 FGFBP1 在 PAAD 中的诊断、预后和治疗意义:UALCAN、TNMplot、OncoDB、GEPIA2、HPA、GSCA、KM Plotter、TISIDB、TISCH2、CancerSEA、STRING、DAVID、细胞培养、RT-qPCR分析、Western印迹分析、集落形成、细胞增殖和伤口愈合试验:结果:表达分析表明,与正常样本相比,PAAD 组织中的 FGFBP1 水平明显升高。启动子甲基化分析表明 PAAD 中甲基化水平较低,与 FGFBP1 表达成反比,提示存在表观遗传调控。遗传变异分析表明,单核苷酸变异对 FGFBP1 的影响不大,但存在拷贝数变异,但不影响 mRNA 的表达。使用 KM plotter 进行的生存期分析表明,FGFBP1 的高表达与总生存期和无病生存期差有关。基于 Cox 回归的预后模型证实了 FGFBP1 升高对患者预后的负面影响。与免疫相关因素的相关性分析表明,FGFBP1可能会造成免疫抑制性肿瘤微环境,影响免疫细胞的浸润和功能。单细胞分析强调了FGFBP1在肿瘤微环境中恶性细胞、内皮细胞和成纤维细胞中的表达。基因富集分析显示,FGFBP1 参与了与癌症进展相关的各种生物过程和通路。使用 RT-qPCR 进行的实验验证证实了 PAAD 细胞系中 FGFBP1 的高表达。在 HEK293T 细胞中敲除 FGFBP1 能显著减少细胞增殖、集落形成和迁移:这些研究结果表明,FGFBP1 在 PAAD 发病机制中起着关键作用,可作为改善患者预后的潜在治疗靶点。
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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.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
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.
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