■痛风是成人最常见的炎症性关节炎。痛风是由尿酸单钠晶体(MSU)在关节中沉积引起的关节炎疾病,这可能导致急性炎症和损伤邻近组织。高尿酸血症是MSU晶体沉积和痛风的主要危险因素。随着痛风疾病负担的增加,目前迫切需要鉴定潜在的生物标志物和新的诊断靶点.
■对于本文的分析,我们从GEO数据库下载了人类痛风数据集GSE160170和痛风小鼠模型数据集GSE190138。为了获得差异表达基因(DEGs),我们将两个数据集相交。使用cytohubba算法,我们确定了关键基因,并通过GO和KEGG对其进行了富集。三个亚组(正常对照组,间歇性痛风组和急性痛风发作组)通过系列聚类(STC)分析进行分析,筛选出关键基因,通过ROC曲线验证诊断效果。分析痛风小鼠背根神经和脊髓关键基因的表达。最后,正常对照组的临床样本,高尿酸血症组,收集间歇性痛风组和急性痛风发作组,酶联免疫吸附试验验证了关键基因在蛋白水平的表达。
■我们通过比较痛风小鼠模型数据集和人类痛风数据集之间的DEG,获得了59个共同上调和28个共同下调的基因。7个集线器DEG(IL1B,通过Cytohubba算法筛选出IL10,NLRP3,SOCS3,PTGS2)。GO和KEGG富集分析的结果表明,7个hub基因在调节炎症反应中起重要作用。免疫反应中的细胞因子产生,和TNF信号通路。通过集群系列试验筛选出最具代表性的hub基因SOCS3和PTGS2,ROC分析结果显示AUC值均高达1.000。此外,我们发现在尿酸单钠(MSU)诱导的痛风小鼠模型中,背根神经节和脊髓中PTGS2的表达显着升高。ELISA结果显示,急性痛风发作组和间歇性痛风组的SOCS3和PTGS2表达明显高于正常对照组。这种差异具有统计学意义,表明群体之间有明显的区别。
■通过跨物种综合分析和实验验证,SOCS3和PTGS2被证明是诊断痛风和预测疾病进展的新生物标志物。
UNASSIGNED: Gout is the most common inflammatory arthritis in adults. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Hyperuricemia is the main risk factor for MSU crystal deposition and gout. With the increasing burden of gout disease, the identification of potential biomarkers and novel targets for diagnosis is urgently needed.
UNASSIGNED: For the analysis of this subject paper, we downloaded the human gout data set GSE160170 and the gout mouse model data set GSE190138 from the GEO database. To obtain the differentially expressed genes (DEGs), we intersected the two data sets. Using the cytohubba algorithm, we identified the key genes and enriched them through GO and KEGG. The gene expression trends of three subgroups (normal control group, intermittent gout group and acute gout attack group) were analyzed by Series Test of Cluster (STC) analysis, and the key genes were screened out, and the diagnostic effect was verified by ROC curve. The expression of key genes in dorsal root nerve and spinal cord of gout mice was analyzed. Finally, the clinical samples of normal control group, hyperuricemia group, intermittent gout group and acute gout attack group were collected, and the expression of key genes at protein level was verified by ELISA.
UNASSIGNED: We obtained 59 co-upregulated and 28 co-downregulated genes by comparing the DEGs between gout mouse model data set and human gout data set. 7 hub DEGs(IL1B, IL10, NLRP3, SOCS3,
PTGS2) were screened out via Cytohubba algorithm. The results of both GO and KEGG enrichment analyses indicate that 7 hub genes play a significant role in regulating the inflammatory response, cytokine production in immune response, and the TNF signaling pathway. The most representative hub genes SOCS3 and
PTGS2 were screened out by Series Test of Cluster, and ROC analysis results showed the AUC values were both up to 1.000. In addition, we found that
PTGS2 expression was significantly elevated in the dorsal root ganglia and spinal cord in monosodium urate(MSU)-induced gout mouse model. The ELISA results revealed that the expression of SOCS3 and
PTGS2 was notably higher in the acute gout attack and intermittent gout groups compared to the normal control group. This difference was statistically significant, indicating a clear distinction between the groups.
UNASSIGNED: Through cross-species comprehensive analysis and experimental verification, SOCS3 and
PTGS2 were proved to be new biomarkers for diagnosing gout and predicting disease progression.