Novel biomarkers associated with oxidative stress and immune infiltration in intervertebral disc degeneration based on bioinformatics approaches

IF 2.6 4区生物学 Q2 BIOLOGY Computational Biology and Chemistry Pub Date : 2024-08-23 DOI:10.1016/j.compbiolchem.2024.108181

Min Xiang , Yue Lai , Jianlin Shen , Bo Wei , Huan Liu , Wenhua Huang

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Abstract

Background

The etiology of intervertebral disc degeneration (IVDD), a prevalent degenerative disease in the elderly, remains to be fully elucidated. The objective of this study was to identify immune infiltration and oxidative stress (OS) biomarkers in IVDD, aiming to provide further insights into the intricate pathogenesis of IVDD.

Methods

The Gene Expression microarrays were obtained from the Gene Expression Omnibus (GEO) database. We conducted enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Subsequently, the R language packages CIBERSORT, MCPcounter, and WGCNA were employed to compare immune infiltration levels between IVDD samples and control samples. A protein-protein interaction (PPI) network was constructed using the Search Tools for the Retrieval of Interacting Genes (STRING) database to identify significant gene clusters. To identify hub genes, we employed Cytoscape's Molecular Complex Detection (MCODE) plug-in. The mRNA levels of hub genes in the cell model were validated by qPCR, while Western blotting was used to validate their protein levels.

Results

The GSE70362 dataset from the GEO database identified a total of 1799 genes that were differentially expressed. Among these, 43 genes were found to be differentially expressed and also associated with OS. The differentially expressed genes associated with OS and the immune-related module genes identified through WGCNA were further intersected, resulting in the identification of 10 key genes that were differentially expressed and played crucial roles in both immune response and OS. Subsequently, we validated four diagnostic markers (PPIA, MAP3K5, PXN, and JAK2) using the GSE122429 external dataset. In a cellular model of OS in NP cells, we have identified the upregulation of PPIA and PXN genes, which could serve as novel markers for IVDD.

Conclusion

The study successfully identified and validated differentially expressed genes associated with oxidative stress and immune infiltration in IVDD samples compared to normal ones. Notably, the newly discovered biomarkers PPIA and PXN have not been previously reported in IVDD-related research.

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基于生物信息学方法的椎间盘退变中与氧化应激和免疫浸润相关的新型生物标记物

背景椎间盘退行性变（IVDD）是一种在老年人中普遍存在的退行性疾病，其病因仍未完全阐明。本研究的目的是鉴定 IVDD 中的免疫浸润和氧化应激（OS）生物标志物，旨在进一步揭示 IVDD 错综复杂的发病机制。我们对基因本体（GO）和京都基因组百科全书（KEGG）术语进行了富集分析。随后，我们使用 R 语言包 CIBERSORT、MCPcounter 和 WGCNA 比较了 IVDD 样本和对照样本之间的免疫浸润水平。利用检索相互作用基因的搜索工具（STRING）数据库构建了蛋白质-蛋白质相互作用（PPI）网络，以确定重要的基因簇。为了识别中心基因，我们使用了Cytoscape的分子复合体检测（MCODE）插件。结果GEO数据库中的GSE70362数据集共发现了1799个差异表达的基因。在这些基因中，有43个基因的差异表达与OS相关。我们将与OS相关的差异表达基因和通过WGCNA鉴定出的免疫相关模块基因进一步交叉，最终确定了10个差异表达的关键基因，这些基因在免疫反应和OS中都起着至关重要的作用。随后，我们利用 GSE122429 外部数据集验证了四个诊断标记（PPIA、MAP3K5、PXN 和 JAK2）。结论该研究成功鉴定并验证了与正常样本相比，IVDD样本中与氧化应激和免疫浸润相关的差异表达基因。值得注意的是，新发现的生物标志物 PPIA 和 PXN 以前从未在 IVDD 相关研究中报道过。

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

Computational Biology and Chemistry 生物-计算机：跨学科应用

CiteScore

6.10

自引率

3.20%

发文量

142

审稿时长

24 days

期刊介绍： Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.