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pmid:36969169
Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy.
Huandi Zhou · Lin Mu · Zhifen Yang · Yonghong Shi
Frontiers in immunology · 2023 doi:10.3389/fimmu.2023.1113212
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Complete file
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KEGG, GO, and GSEA analyses were performed. Hub genes were screened by conducting PPI networks and calculating node genes using five algorithms with CytoHubba, followed by LASSO and ROC analysis to accurately identify diagnostic biomarkers. In addition, two different GEO datasets, GSE175759 and GSE47184, and an experiment cohort with 30 controls and 40 DN patients detected by IHC, were used to validate the biomarkers. Moreover, ssGSEA was performed to analyze the immune microenvironment in DN. Wilcoxon test and LASSO regression were used to determine the core immune signatures. The correlation between biomarkers and crucial immune signatures was calculated by Spearman analysis. Finally, cMap was used to explore potential drugs treating renal tubule injury in DN patients.\nResults: A total of 509 DEGs, including 338 upregulated and 171 downregulated genes, were screened out. \"chemokine signaling pathway\" and \"cell adhesion molecules\" were enriched in both GSEA and KEGG analysis. CCR2, CX3CR1, and SELP, especially for the combination model of the three genes, were identified as core biomarkers with high diagnostic capabilities with striking AUC, sensitivity, and specificity in both merged and validated datasets and IHC validation. Immune infiltration analysis showed a notable infiltration advantage for APC co-stimulation, CD8+ T cells, checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation in the DN group. In addition, the correlation analysis showed that CCR2, CX3CR1, and SELP were strongly and positively correlated with checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation in the DN group. Finally, dilazep was screened out as an underlying compound for DN analyzed by CMap.\nConclusions: CCR2, CX3CR1, and SELP are underlying diagnostic biomarkers for DN, especially in their combination. APC co-stimulation, CD8+ T cells, checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation may participate in the occurrence and development of DN. At last, dilazep may be a promising drug for treating DN.", "claims": [{"id": "claim-method", "statement": "To validate the diagnostic of six hub genes, ROC was conducted to calculate the AUC, specificity, and sensitivity.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36969169", "locator": "sections[18] \"Diagnostic effectiveness of six hub genes and validation of screened core genes\" paragraph 2", "quote": "To validate the diagnostic of six hub genes, ROC was conducted to calculate the AUC, specificity, and sensitivity."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . 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