基于综合生物信息学分析的 SSR1 和 CKAP4--椎间盘退变的潜在生物标记物

IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine Pub Date : 2023-12-20 DOI:10.1002/jsp2.1309
Danqing Guo, Min Zeng, Miao Yu, Jingjing Shang, Jinxing Lin, Lichu Liu, Kuangyang Yang, Zhenglin Cao
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引用次数: 0

摘要

椎间盘变性(IDD)是导致腰背痛的一个重要原因,也是一个重大的公共卫生问题。本研究的目的是利用综合生物信息学方法确定潜在的 IDD 相关生物标志物,并在体外进行验证。在本研究中,我们采用了多种分析方法来确定参与 IDD 的关键基因。我们利用加权基因共表达网络分析(WGCNA)、MCODE、LASSO算法和ROC曲线来确定关键基因。此外,我们还利用免疫浸润分析和单细胞测序数据集进一步探索了关键基因的特征。最后,我们在人体椎间盘组织上进行了体外实验,以验证这些关键基因在 IDD 中的重要性。我们从 GEO 数据库(GSE23130 和 GSE15227)中获得了基因表达谱,并确定了 1015 个与 IDD 相关的 DEGs。利用 WGCNA,我们确定了与 IDD 显著相关的蓝色模块。在 DEGs 中,根据 |logFC| ≥ 2.0 和 p.adj <0.05 的标准,我们发现了 47 个与蓝色模块中的基因重叠的枢纽基因。利用 MCODE 和 LASSO 算法进行的进一步分析使我们确定了五个关键基因,其中 CKAP4 和 SSR1 通过 GSE70362 验证,对 IDD 有显著的诊断价值。此外,免疫浸润分析表明,单核细胞与这两个关键基因显著相关。我们还分析了单细胞测序数据集 GSE199866,该数据集显示 CKAP4 和 SSR1 在纤维软骨软骨细胞中均有高表达。最后,我们对 30 个人体椎间盘样本进行了实时聚合酶链反应(RT-PCR)和免疫组化(IHC),在体外验证了我们的发现。结果显示,CKAP4 和 SSR1 在退化的椎间盘样本中上调。综上所述,我们的研究结果表明,CKAP4和SSR1有可能成为IDD的疾病生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

SSR1 and CKAP4 as potential biomarkers for intervertebral disc degeneration based on integrated bioinformatics analysis

SSR1 and CKAP4 as potential biomarkers for intervertebral disc degeneration based on integrated bioinformatics analysis

Background

Intervertebral disc degeneration (IDD) is a significant cause of low back pain and poses a significant public health concern. Genetic factors play a crucial role in IDD, highlighting the need for a better understanding of the underlying mechanisms.

Aim

The aim of this study was to identify potential IDD-related biomarkers using a comprehensive bioinformatics approach and validate them in vitro.

Materials and Methods

In this study, we employed several analytical approaches to identify the key genes involved in IDD. We utilized weighted gene coexpression network analysis (WGCNA), MCODE, LASSO algorithms, and ROC curves to identify the key genes. Additionally, immune infiltrating analysis and a single-cell sequencing dataset were utilized to further explore the characteristics of the key genes. Finally, we conducted in vitro experiments on human disc tissues to validate the significance of these key genes in IDD.

Results

we obtained gene expression profiles from the GEO database (GSE23130 and GSE15227) and identified 1015 DEGs associated with IDD. Using WGCNA, we identified the blue module as significantly related to IDD. Among the DEGs, we identified 47 hub genes that overlapped with the genes in the blue module, based on criteria of |logFC| ≥ 2.0 and p.adj <0.05. Further analysis using both MCODE and LASSO algorithms enabled us to identify five key genes, of which CKAP4 and SSR1 were validated by GSE70362, demonstrating significant diagnostic value for IDD. Additionally, immune infiltrating analysis revealed that monocytes were significantly correlated with the two key genes. We also analyzed a single-cell sequencing dataset, GSE199866, which showed that both CKAP4 and SSR1 were highly expressed in fibrocartilage chondrocytes. Finally, we validated our findings in vitro by performing real time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) on 30 human disc samples. Our results showed that CKAP4 and SSR1 were upregulated in degenerated disc samples. Taken together, our findings suggest that CKAP4 and SSR1 have the potential to serve as disease biomarkers for IDD.

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来源期刊
JOR Spine
JOR Spine ORTHOPEDICS-
CiteScore
6.40
自引率
18.90%
发文量
42
审稿时长
10 weeks
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