Systematic identification of key extracellular proteins as the potential biomarkers in lupus nephritis

作者：Xue Zhou, Yuefeng Zhang, Ning Wang · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.915784 · 被引用次数：38 · 研究领域：Systemic Lupus Erythematosus Research、Renal Diseases and Glomerulopathies、Chronic Kidney Disease and Diabetes

Background: Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE) with considerable morbidity/mortality and limited treatment options. Since kidney biopsy is a relative hysteretic indicator, it is indispensable to investigate potential biomarkers for early diagnosis and predicting clinical outcomes of LN patients. Extracellular proteins may become the promising biomarkers by the secretion into body fluid. Our study linked extracellular proteins with lupus nephritis to identify the emerging biomarkers. Methods: the protein-protein interaction (PPI) network. The expression level, immune characteristics, and diagnostic value of these candidate biomarkers were investigated. Finally, the Nephroseq V5 tool was applied to evaluate the clinical significance of the key EP-DEGs. Results: A total of 164 DEGs were acquired by comparing LN samples with healthy controls based on GSE32591 datasets. Then, 38 EP-DEGs were screened out through the intersection between DEGs and extracellular protein gene lists. Function enrichment analysis indicated that these EP-DEGs might participate in immune response and constitute the extracellular matrix. Four key EP-DEGs (LUM, TGFBI, COL1A2, and POSTN) were eventually identified as candidate biomarkers, and they were all overexpressed in LN samples. Except that LUM expression was negatively correlated with most of the immune regulatory genes, there was a positive correlation between the remaining ...