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验证新的免疫和炎症相关的 RA 诊断生物标志物。

Validation of new immune and inflammation-related diagnostic biomarkers for RA.

机构信息

Department of Rheumatology, Hexian People's Hospital, Ma'anshan City, Anhui Province, China.

出版信息

Clin Rheumatol. 2024 Mar;43(3):949-958. doi: 10.1007/s10067-024-06882-y. Epub 2024 Jan 29.

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease, whose development is associated with immune cells and persistent inflammation. Exploring the biomarkers of RA holds immense significance in terms of the prevention, diagnosis, and treatment of RA.

MATERIAL AND METHODS

The differentially expressed genes (DEGs) in RA patients and the control group were screened by limma package. Through DEGs intersection overlapping 200 inflammatory response-related genes and 2498 immune-related genes, differentially expressed immune and inflammation-related genes (DE-IIRGs) were identified. Lasso regression analysis screened RA diagnostic biomarkers and constructed PPI networks. Finally, immune infiltration analysis and drug prediction were performed.

RESULTS

A total of 20 DE-IIRGs were identified by overlapping DEGs with 2498 immune-related genes and 200 inflammatory response-related genes. These DE-IIRGs were primarily enriched in the cytokine-cytokine receptor interaction and other biological processes, and then five biomarker genes (TNFSF10, IL1R1, CXCL9, ACVR1B, and IL15) were identified. It was found that the expression levels of CXCL9, IL15, and TNFSF10 in the disease samples were significantly higher than those in the control group. These biomarker genes have more effective diagnostic potential. The RA samples exhibited significantly higher levels of cell infiltration compared to the control samples. hsa-miR-199a-5p's connections to the ACVR1B and CCR7 genes were identified by creating ceRNA networks from 20 screened DE-IIRGs. There was a connection between CCL5 and AEMA4D and hsa-miR-214-3p.

CONCLUSION

We identified immune- and inflammation-related biomarkers in RA based on bioinformatics analysis and screened TNFSF10, IL1R1, CXCL9, ACVR1B, and IL15 as diagnostic markers for RA. Key Points • TNFSF10, IL1R1, CXCL9, ACVR1B, and IL15 may be new diagnostic biomarkers for RA. • These findings may provide a theoretical basis for early RA diagnosis.

摘要

背景

类风湿关节炎(RA)是一种慢性、系统性自身免疫性疾病,其发展与免疫细胞和持续炎症有关。探索 RA 的生物标志物对于 RA 的预防、诊断和治疗具有重要意义。

材料和方法

通过 limma 包筛选 RA 患者和对照组的差异表达基因(DEGs)。通过 DEGs 与 2498 个免疫相关基因和 200 个炎症反应相关基因的交集重叠,鉴定出差异表达的免疫和炎症相关基因(DE-IIRGs)。通过 Lasso 回归分析筛选 RA 诊断生物标志物并构建 PPI 网络。最后进行免疫浸润分析和药物预测。

结果

通过与 2498 个免疫相关基因和 200 个炎症反应相关基因的 DEGs 重叠,共鉴定出 20 个 DE-IIRGs。这些 DE-IIRGs 主要富集在细胞因子-细胞因子受体相互作用和其他生物学过程中,然后鉴定出 5 个生物标志物基因(TNFSF10、IL1R1、CXCL9、ACVR1B 和 IL15)。结果发现,疾病样本中 CXCL9、IL15 和 TNFSF10 的表达水平明显高于对照组。这些生物标志物基因具有更高的诊断潜力。与对照组样本相比,RA 样本的细胞浸润水平显著升高。通过从 20 个筛选出的 DE-IIRGs 中构建 ceRNA 网络,发现 hsa-miR-199a-5p 与 ACVR1B 和 CCR7 基因的连接。发现 CCL5 与 AEMA4D 和 hsa-miR-214-3p 的连接。

结论

我们通过生物信息学分析鉴定了 RA 中的免疫和炎症相关生物标志物,并筛选出 TNFSF10、IL1R1、CXCL9、ACVR1B 和 IL15 作为 RA 的诊断标志物。

关键点

  • TNFSF10、IL1R1、CXCL9、ACVR1B 和 IL15 可能是 RA 的新诊断生物标志物。

  • 这些发现可能为早期 RA 诊断提供理论依据。

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