Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study.

IF 2.7 3区 生物学
Fuchuan Jiang, Sajjad Ahmad, Sadia Kanwal, Yasir Hameed, Qian Tang
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引用次数: 0

Abstract

Background: Uterine Corpus Endometrial Carcinoma (UCEC) is a prevalent gynecologic malignancy with complex molecular underpinnings. This study identifies key woundhealing genes involved in UCEC and elucidates their roles through a comprehensive analysis.

Methods: In silico and in vitro experiments.

Results: Seventy wound healing-associated genes were extracted from the Gene Ontology (GO) database, and a protein-protein interaction (PPI) network was constructed using the STRING database. CytoHubba analysis in Cytoscape identified six pivotal hub genes: CD44, FGF2, FGF10, KDM6A, FN1, and MMP2. These genes exhibited significantly lower expression in UCEC cell lines compared to normal controls, as confirmed by RT-qPCR. Receiver Operating Characteristic (ROC) analysis demonstrated their potential as diagnostic biomarkers, with Area Under the Curve (AUC) values ranging from 0.94 to 1.00. Validation using TCGA datasets revealed consistent downregulation of these genes in UCEC samples, corroborated by immunohistochemical staining. Promoter methylation analysis showed significantly higher methylation levels in UCEC, correlating with decreased mRNA expression and poor survival outcomes. Genetic alteration analysis indicated frequent mutations in FN1 and KDM6A, although these did not significantly affect survival. Functional analysis using the CancerSEA database highlighted the involvement of these genes in critical cancer-related processes, including angiogenesis, apoptosis, and metastasis. Immune correlation studies revealed significant associations with immune inhibitor genes and distinct expression patterns across immune subtypes. Overexpression studies in UCEC cell lines demonstrated that CD44 and MMP2 reduce proliferative ability while enhancing migration and wound healing.

Conclusion: Collectively, these findings underscore the crucial roles of CD44, FGF2, FGF10, KDM6A, FN1, and MMP2 in UCEC pathogenesis, highlighting their potential as biomarkers and therapeutic targets in this malignancy.

关键伤口愈合基因作为子宫内膜癌的诊断生物标志物和治疗靶点:一项综合的计算机和体外研究。
背景:子宫体子宫内膜癌(UCEC)是一种常见的妇科恶性肿瘤,具有复杂的分子基础。本研究确定了UCEC中涉及的关键伤口愈合基因,并通过综合分析阐明了它们的作用。方法:计算机实验和体外实验。结果:从基因本体(Gene Ontology, GO)数据库中提取了70个伤口愈合相关基因,并利用STRING数据库构建了蛋白-蛋白相互作用(protein-protein interaction, PPI)网络。Cytoscape中的CytoHubba分析鉴定出6个关键枢纽基因:CD44、FGF2、FGF10、KDM6A、FN1和MMP2。RT-qPCR证实,与正常对照相比,这些基因在UCEC细胞系中的表达明显降低。受试者工作特征(ROC)分析显示了它们作为诊断生物标志物的潜力,曲线下面积(AUC)值从0.94到1.00不等。使用TCGA数据集的验证显示,这些基因在UCEC样本中一致下调,免疫组织化学染色证实了这一点。启动子甲基化分析显示,UCEC中甲基化水平显著升高,这与mRNA表达减少和生存预后差有关。基因改变分析表明,FN1和KDM6A频繁突变,尽管这些突变对生存率没有显著影响。使用CancerSEA数据库的功能分析强调了这些基因参与关键的癌症相关过程,包括血管生成、细胞凋亡和转移。免疫相关研究揭示了免疫抑制剂基因与免疫亚型之间的显著关联和不同的表达模式。UCEC细胞系的过表达研究表明,CD44和MMP2在促进迁移和伤口愈合的同时降低了增殖能力。结论:总的来说,这些发现强调了CD44、FGF2、FGF10、KDM6A、FN1和MMP2在UCEC发病机制中的关键作用,强调了它们作为这种恶性肿瘤的生物标志物和治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hereditas
Hereditas Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.80
自引率
3.70%
发文量
0
期刊介绍: For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.
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