Identification and Analysis of Potential Biomarkers Associated with Neutrophil Extracellular Traps in Cervicitis.

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2024-10-17 DOI:10.1007/s10528-024-10919-x

Wantao Liang, Yanyuan Bai, Hua Zhang, Yan Mo, Xiufang Li, Junming Huang, Yangliu Lei, Fangping Gao, Mengmeng Dong, Shan Li, Juan Liang

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引用次数: 0

Abstract

Early diagnosis of cervicitis is important. Previous studies have found that neutrophil extracellular traps (NETs) play pro-inflammatory and anti-inflammatory roles in many diseases, suggesting that they may be involved in the inflammation of the uterine cervix and NETs-related genes may serve as biomarkers of cervicitis. However, what NETs-related genes are associated with cervicitis remains to be determined. Transcriptome analysis was performed using samples of exfoliated cervical cells from 15 patients with cervicitis and 15 patients without cervicitis as the control group. First, the intersection of differentially expressed genes (DEGs) and neutrophil extracellular trap-related genes (NETRGs) were taken to obtain genes, followed by functional enrichment analysis. We obtained hub genes through two machine learning algorithms. We then performed Artificial Neural Network (ANN) and nomogram construction, confusion matrix, receiver operating characteristic (ROC), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Moreover, we constructed ceRNA network, mRNA-transcription factor (TF) network, and hub genes-drug network. We obtained 19 intersecting genes by intersecting 1398 DEGs and 136 NETRGs. 5 hub genes were obtained through 2 machine learning algorithms, namely PKM, ATG7, CTSG, RIPK3, and ENO1. Confusion matrix and ROC curve evaluation ANN model showed high accuracy and stability. A nomogram containing the 5 hub genes was established to assess the disease rate in patients. The correlation analysis revealed that the expression of ATG7 was synergistic with RIPK3. The GSEA showed that most of the hub genes were related to ECM receptor interactions. It was predicted that the ceRNA network contained 2 hub genes, 3 targeted miRNAs, and 27 targeted lnRNAs, and that 5 mRNAs were regulated by 28 TFs. In addition, 36 small molecule drugs that target hub genes may improve the treatment of cervicitis. In this study, five hub genes (PKM, ATG7, CTSG, RIPK3, ENO1) provided new directions for the diagnosis and treatment of patients with cervicitis.

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宫颈炎中与中性粒细胞胞外陷阱相关的潜在生物标记物的鉴定与分析

宫颈炎的早期诊断非常重要。以往的研究发现，中性粒细胞胞外捕获物（NETs）在许多疾病中起到促炎和抗炎的作用，这表明它们可能参与了子宫颈的炎症，NETs相关基因可能成为宫颈炎的生物标志物。然而，哪些NET相关基因与宫颈炎有关仍有待确定。研究人员以 15 名宫颈炎患者和 15 名无宫颈炎患者的脱落宫颈细胞样本为对照组，进行了转录组分析。首先，取差异表达基因（DEGs）和中性粒细胞胞外陷阱相关基因（NETRGs）的交叉点获得基因，然后进行功能富集分析。我们通过两种机器学习算法获得了中枢基因。然后，我们进行了人工神经网络（ANN）和提名图构建、混淆矩阵、接收者操作特征（ROC）、基因组富集分析（GSEA）和免疫细胞浸润分析。此外，我们还构建了 ceRNA 网络、mRNA-转录因子（TF）网络和枢纽基因-药物网络。我们通过交叉 1398 个 DEGs 和 136 个 NETRGs 获得了 19 个交叉基因。通过2种机器学习算法获得了5个枢纽基因，分别是PKM、ATG7、CTSG、RIPK3和ENO1。混淆矩阵和 ROC 曲线评估表明，ANN 模型具有较高的准确性和稳定性。建立了一个包含 5 个枢纽基因的提名图来评估患者的患病率。相关性分析表明，ATG7的表达与RIPK3具有协同作用。GSEA显示，大多数中心基因与ECM受体相互作用有关。据预测，ceRNA网络包含2个枢纽基因、3个靶向miRNA和27个靶向lnRNA，5个mRNA受28个TFs调控。此外，36种靶向枢纽基因的小分子药物可能会改善宫颈炎的治疗。在这项研究中，5个枢纽基因（PKM、ATG7、CTSG、RIPK3、ENO1）为宫颈炎患者的诊断和治疗提供了新的方向。

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

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.