Department of Clinical Pharmacy, Zibo Central Hospital, Zibo, Shandong, China.
Department of Pharmacy, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Front Immunol. 2023 Sep 29;14:1231611. doi: 10.3389/fimmu.2023.1231611. eCollection 2023.
Systemic lupus erythematosus (SLE) is an autoimmune disease involving many systems and organs, and individuals with SLE exhibit unique cancer risk characteristics. The significance of the basement membrane (BM) in the occurrence and progression of human autoimmune diseases and tumors has been established through research. However, the roles of BM-related genes and their protein expression mechanisms in the pathogenesis of SLE and pan-cancer development has not been elucidated.
In this study, we applied bioinformatics methods to perform differential expression analysis of BM-related genes in datasets from SLE patients. We utilized LASSO logistic regression, SVM-RFE, and RandomForest to screen for feature genes and construct a diagnosis model for SLE. In order to attain a comprehensive comprehension of the biological functionalities of the feature genes, we conducted GSEA analysis, ROC analysis, and computed levels of immune cell infiltration. Finally, we sourced pan-cancer expression profiles from the TCGA and GTEx databases and performed pan-cancer analysis.
We screened six feature genes (AGRN, PHF13, SPOCK2, TGFBI, COL4A3, and COLQ) to construct an SLE diagnostic model. Immune infiltration analysis showed a significant correlation between AGRN and immune cell functions such as parainflammation and type I IFN response. After further gene expression validation, we finally selected AGRN for pan-cancer analysis. The results showed that AGRN's expression level varied according to distinct tumor types and was closely correlated with some tumor patients' prognosis, immune cell infiltration, and other indicators.
In conclusion, BM-related genes play a pivotal role in the pathogenesis of SLE, and AGRN shows immense promise as a target in SLE and the progression of multiple tumors.
系统性红斑狼疮(SLE)是一种涉及多个系统和器官的自身免疫性疾病,SLE 患者具有独特的癌症风险特征。通过研究已经证实,基底膜(BM)在人类自身免疫性疾病和肿瘤的发生和发展中具有重要意义。然而,BM 相关基因及其蛋白表达机制在 SLE 和泛癌发展中的作用尚未阐明。
本研究应用生物信息学方法对来自 SLE 患者的数据集进行 BM 相关基因的差异表达分析。我们利用 LASSO 逻辑回归、SVM-RFE 和 RandomForest 筛选特征基因,并构建 SLE 的诊断模型。为了全面了解特征基因的生物学功能,我们进行了 GSEA 分析、ROC 分析和免疫细胞浸润水平的计算。最后,我们从 TCGA 和 GTEx 数据库中获取泛癌表达谱,并进行泛癌分析。
我们筛选了六个特征基因(AGRN、PHF13、SPOCK2、TGFBI、COL4A3 和 COLQ)来构建 SLE 诊断模型。免疫浸润分析表明 AGRN 与副炎症和 I 型 IFN 反应等免疫细胞功能之间存在显著相关性。经过进一步的基因表达验证,我们最终选择 AGRN 进行泛癌分析。结果表明,AGRN 的表达水平根据不同的肿瘤类型而变化,与某些肿瘤患者的预后、免疫细胞浸润等指标密切相关。
综上所述,BM 相关基因在 SLE 的发病机制中起着关键作用,AGRN 作为 SLE 和多种肿瘤进展的靶点具有巨大的潜力。