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通过生物信息学分析筛选和验证瘢痕疙瘩的诊断标志物

Screening and validation of diagnostic markers for keloids via bioinformatics analysis.

作者信息

Wang Ze, Hu Bo, Li Wenfei, Ma Tengxiao, Li Lei

机构信息

Hainan Affiliated Hospital of Hainan Medical University, Hainan, Haikou, 570100, China.

出版信息

Biochem Biophys Rep. 2025 Aug 22;43:102219. doi: 10.1016/j.bbrep.2025.102219. eCollection 2025 Sep.

Abstract

BACKGROUND

Keloid (KD) disease is a skin lesions caused by abnormal wound healing that involve complex cellular and molecular mechanisms. The aim of this study was to screen diagnostic markers of KD via bioinformatics methods and evaluate their clinical application value.

METHODS

The GSE44270, GSE145725, GSE7890 and GSE83286 datasets were analyzed in combination with difference analysis and weighted gene coexpression network analysis (WGCNA) and machine learning algorithms, candidate genes related to KD were screened and verified via receiver operating characteristic (ROC) curves and external datasets. KD samples were classified by consistent clustering, and the infiltration of immune cells was investigated. Simultaneously, a diagnostic biomarker-related ceRNA network was constructed. Drug small molecules and compounds were predicted online, and molecular docking was performed. Finally, RT‒qPCR and WB were used to verify the expression of the markers.

RESULTS

In this study, two upregulated genes, SMURF2 and CCDC80, which are significantly associated with a variety of immune cells, were screened. KD was divided into the C1 and C2 subtypes, SMURF2 was highly expressed in C1, and CCDC80 was highly expressed in C2. Drug prediction and molecular docking analysis suggest that bisphenol A may have a potential effect on KD therapy. RT‒qPCR and WB revealed that the mRNA and protein expression levels of SMURF2 and CCDC80 in KD samples were significantly increased.

CONCLUSION

Our study identified two genes that may be used as diagnostic markers of KD, providing new perspectives and potential molecular targets for the study of the molecular mechanisms and clinical diagnosis of KD.

摘要

背景

瘢痕疙瘩(KD)疾病是一种由异常伤口愈合引起的皮肤病变,涉及复杂的细胞和分子机制。本研究的目的是通过生物信息学方法筛选KD的诊断标志物,并评估其临床应用价值。

方法

结合差异分析、加权基因共表达网络分析(WGCNA)和机器学习算法对GSE44270、GSE145725、GSE7890和GSE83286数据集进行分析,通过受试者工作特征(ROC)曲线和外部数据集筛选并验证与KD相关的候选基因。通过一致性聚类对KD样本进行分类,并研究免疫细胞的浸润情况。同时,构建与诊断生物标志物相关的ceRNA网络。在线预测药物小分子和化合物,并进行分子对接。最后,采用RT-qPCR和WB验证标志物的表达。

结果

在本研究中,筛选出两个上调基因SMURF2和CCDC80,它们与多种免疫细胞显著相关。KD分为C1和C2亚型,SMURF2在C1中高表达,CCDC80在C2中高表达。药物预测和分子对接分析表明,双酚A可能对KD治疗有潜在作用。RT-qPCR和WB显示,KD样本中SMURF2和CCDC80的mRNA和蛋白表达水平显著升高。

结论

我们的研究鉴定出两个可能用作KD诊断标志物的基因,为KD的分子机制研究和临床诊断提供了新的视角和潜在的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7027/12420520/6757e0fdb737/gr1.jpg

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