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泛癌视角下VEGF-B基因在人类肿瘤中的致癌作用研究

The oncogenic role of VEGF-B gene in human tumors from a pan-cancer perspective
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摘要 目的旨在对血管内皮生长因子B(VEGF-B)基因进行泛癌分析,探讨其在不同癌症类型中的表达模式、功能及其与临床病理特征的关系,为VEGF-B在癌症诊断、预后评估和治疗靶点选择中的应用提供思路。方法采用多种生物信息学方法,包括遗传变异分析、基因表达分析、蛋白表达分析、免疫浸润分析、生存预后分析、临床特征相关性分析、蛋白质-蛋白质相互作用(PPI)网络及富集分析,对癌症基因组图谱(TCGA)、肿瘤免疫系统相互作用数据库(TISIDB)、癌症基因组学门户网站(cBioPortal)等数据库中的数据进行综合分析。结果VEGF-B在子宫癌肉瘤中的突变频率最高(>10%),突变类型主要为扩增,且与患者的总体生存期显著相关(P<0.05)。VEGF-B在多种癌症中表达升高,包括胆管癌、结肠癌、多形成性胶质细胞瘤、头颈鳞状细胞癌、肾癌、肝癌和嗜铬细胞瘤等,且其表达水平与肿瘤的临床分期显著相关(P<0.05)。VEGF-B表达与成纤维细胞和NK细胞的免疫浸润呈正相关(P<0.05),而与辅助性T细胞和中央记忆型T细胞的免疫浸润呈负相关(P<0.05)。VEGF-B的过度表达与肾上腺皮质癌、膀胱癌和结直肠癌患者的总体生存率不良预后相关(P<0.05)。VEGF-B与PI3K-Akt和MAPK信号通路中的多个分子存在相互作用,这些通路在肿瘤发生中起关键作用。基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析进一步证实了VEGF-B在血管生成、细胞增殖和信号传导中的作用。结论VEGF-B在人类肿瘤中发挥重要作用,可能作为潜在的生物标志物和治疗靶点。未来研究应通过实验验证VEGF-B的功能性影响,并探讨其在临床治疗中的应用潜力。 Objective To conduct a pan-cancer analysis of the vascular endothelial growth factor B(VEGF-B)gene,exploring its expression patterns,functions,and associations with clinical pathological features across different cancer types.This research is intended to provide insights into the potential applications of VEGF-B in cancer diagnosis,prognosis evaluation,and therapeutic target selection.Methods A comprehensive analysis was performed using various bioinformatics approaches,including genetic variation analysis,gene express ion analysis,protein expression analysis,immune infiltration analysis,survival prognosis analysis,clinical feature correlation analysis,protein-protein interaction(PPI)network analysis,and enrichment analysis.Data from multiple databases,such as The gancer genome atlas(TCGA),tumor-immune system interaction database(TISIDB),and cBio cancer genomics portal(cBioPortal),were integrated for this study.Results The mutation frequency of VEGF-B was highest in uterine carcinosarcoma(>10%),with amplification being the predominant mutation type.This mutation was significantly associated with overall survival(P<0.05).Elevated expression of VEGF-B was observed in various cancers,including cholangiocarcinoma,colorectal cancer,glioblastoma,head and neck squamous cell carcinoma,renal cancer,liver cancer,and pheochromocytoma.The expression levels of VEGF-B were significantly correlated with tumor clinical stages(P<0.05).Additionally,VEGF-B expression was positively correlated with the immune infiltration of fibroblasts and NK cells(P<0.05),while negatively correlated with the infiltration of helper T cells and central memory T cells(P<0.05).Overexpression of VEGF-B was associated with poor overall survival prognosis in patients with adrenocortical carcinoma,bladder cancer,and colorectal cancer(P<0.05).VEGF-B interacted with multiple molecules in the PI3K-Akt and MAPK signaling pathways,which play key roles in tumorigenesis.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses further confirmed the roles of VEGF-B in angiogenesis,cell proliferation,and signal transduction.Conclusion VEGF-B plays a significant role in human tumors and may serve as a potential biomarker and therapeutic target.Future studies should experimentally validate the functional impact of VEGF-B and explore its potential applications in clinical therapy.
作者 董鑫宇 景宝 刘琪 宣言 王慕宁 常思瑶 张博健 王胜 林雨丰 韩志阳 DONG Xinyu;JING Bao;LIU Qi;XUAN Yan;WANG Muning;CHANG Siyao;ZHANG Bojian;WANG Sheng;LIN Yufeng;HAN Zhiyang(Department of Vascular Surgery,the First Affiliated Hospital of Harbin Medical University,Heilongjiang,Harbin 150001,China;Department of Medical Laboratory Science and Technology,Harbin Medical University Daqing,Heilongjiang,Daqing 163000,China;Department of Thyroid,Breast and Vascular Surgery,the Second Hospital of Harbin,Heilongjiang,Harbin 150056,China)
出处 《中国医药科学》 2025年第21期10-17,29,共9页 China Medicine And Pharmacy
基金 黑龙江省博士后科研基金(LBH-Q21135)。
关键词 血管内皮生长因子B 肿瘤 预后 免疫 生物标志物 Vascular endothelial growth factor B Cancer Prognosis Immunity Biomarker
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