膀胱癌（BLCA）是全球最常见的恶性肿瘤之一。目前尚无经验证的生物标志物可用于辅助诊断该癌症的治疗。DNA甲基化修饰在表观遗传学中起着重要作用。鉴定甲基化差异表达基因是发现生物标志物的常用方法。本研究从基因表达数据库（GEO）中获取了膀胱癌数据，包括基因表达芯片GSE37817（18例患者和3例正常人）、GSE52519（9例患者和3例正常人）以及基因甲基化芯片GSE37816（18例患者和3例正常人）。通过GEO2R获取了异常表达基因。使用DAVID数据库和KOBAS分析了基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径。使用STRING和Cytoscape软件构建了蛋白质-蛋白质相互作用（PPI）和关键基因网络。通过Gene Expression Profiling Interactive Analysis（GEPIA）、Gene Set Cancer Analysis（GSCA）、cBioProtal和MEXPRESS等4个在线平台对结果进行了验证。总共鉴定了GSE37817和GSE52519分别具有253个和298个上调基因以及674个和454个下调基因。对于GSE37816数据集，观察到涉及778个高甲基化基因和3420个低甲基化基因。17个高甲基化低表达基因富集在不同器官发育和形态发生相关的生物过程中。在分子功能方面，这些基因在细胞外基质结构成分中表现出富集。途径富集显示药物代谢酶和几种氨基酸代谢、PI3K-Akt、Hedgehog信号通路。Cytoscape软件筛选的前3个关键基因为EFEMP1、SPARCL1和ABCA8。通过GEPIA、GSCA、cBioProtal和EXPRESS数据库验证了研究结果，并且验证了关键高甲基化低表达基因。本研究通过综合生物信息学分析筛选了BLCA中潜在的异常甲基化表达关键基因。研究结果可能为未来BLCA的精确诊断和治疗提供可能的甲基化基础的生物标志物。© 2023. BioMed Central Ltd.是Springer Nature的一部分。

Bladder cancer (BLCA) is one of the most common malignancies among tumors worldwide. There are no validated biomarkers to facilitate such treatment diagnosis. DNA methylation modification plays important roles in epigenetics. Identifying methylated differentially expressed genes is a common method for the discovery of biomarkers.Bladder cancer data were obtained from Gene Expression Omnibus (GEO), including the gene expression microarrays GSE37817( 18 patients and 3 normal ), GSE52519 (9 patients and 3 normal) and the gene methylation microarray GSE37816 (18 patients and 3 normal). Aberrantly expressed genes were obtained by GEO2R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using the DAVID database and KOBAS. Protein-protein interactions (PPIs) and hub gene networks were constructed by STRING and Cytoscape software. The validation of the results which was confirmed through four online platforms, including Gene Expression Profiling Interactive Analysis (GEPIA), Gene Set Cancer Analysis (GSCA), cBioProtal and MEXPRESS.In total, 253 and 298 upregulated genes and 674 and 454 downregulated genes were identified for GSE37817 and GSE52519, respectively. For the GSE37816 dataset, hypermethylated and hypomethylated genes involving 778 and 3420 genes, respectively, were observed. Seventeen hypermethylated and low expression genes were enriched in biological processes associated with different organ development and morphogenesis. For molecular function, these genes showed enrichment in extracellular matrix structural constituents. Pathway enrichment showed drug metabolic enzymes and several amino acids metabolism, PI3K-Akt, Hedgehog signaling pathway. The top 3 hub genes screened by Cytoscape software were EFEMP1, SPARCL1 and ABCA8. The research results were verified using the GEPIA, GSCA, cBioProtal and EXPRESS databases, and the hub hypermethylated low expression genes were validated.This study screened possible aberrantly methylated expression hub genes in BLCA by integrated bioinformatics analysis. The results may provide possible methylation-based biomarkers for the precise diagnosis and treatment of BLCA in the future.© 2023. BioMed Central Ltd., part of Springer Nature.