Identification of Key Biomarkers and Immune Infiltration in Sciatic Nerve of Diabetic Neuropathy BKS-db/db Mice by Bioinformatics Analysis.

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In order to determine the key genes and pathways related to the pathogenesis of DN, we downloaded the microarray data set GSE27382 from Gene Expression Omnibus (GEO) and adopted bioinformatics methods for comprehensive analysis, including functional enrichment, construction of PPI networks, central genes screening, TFs-target interaction analysis, and evaluation of immune infiltration characteristics. Finally, we examined quantitative real- time PCR (qPCR) to validate the expression of hub genes. A total of 318 differentially expressed genes (DEGs) were identified, among which 125 upregulated DEGs were enriched in the mitotic nuclear division, extracellular region, immunoglobulin receptor binding, and p53 signaling pathway, while 193 downregulated DEGs were enriched in ion transport, membrane, synapse, sodium channel activity, and retrograde endocannabinoid signaling. GSEA plots showed that condensed nuclear chromosome kinetochore were the most significant enriched gene set positively correlated with the DN group. Importantly, we identified five central genes (Birc5, Bub1, Cdk1, Ccnb2, and Ccnb1), and KEGG pathway analysis showed that the five hub genes were focused on progesterone-mediated oocyte maturation, cell cycle, and p53 signaling pathway. The proportion of immune cells from DN tissue and normal group showed significant individual differences. In DN samples, T cells CD4 memory resting and dendritic cells resting accounted for a higher proportion, and macrophage M2 accounted for a lower proportion. In addition, all five central genes showed consistent correlation with immune cell infiltration levels. qPCR showed the same expression trend of five central genes as in our analysis. Our research identified key genes related to differential genes and immune infiltration related to the pathogenesis of DN and provided new diagnostic and potential therapeutic targets for DN.", "claims": [{"id": "claim-method", "statement": "Finally, we used the Pearson method to analyze the relationship between immune cells and core gene expression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34122109", "locator": "sections[10] \"Determination of Immune Cell Landscapes\" paragraph 2", "quote": "Finally, we used the Pearson method to analyze the relationship between immune cells and core gene expression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM677105", "GSM677106", "GSM677107", "GSM677108", "GSM677109", "GSM677110", "GSM677111", "GSM677112", "GSM677113", "GSM677114", "GSM677115", "GSM677116", "GSM677117"], "sample_count": 13, "group_sizes": null, "group_sizes_basis": null, "platform": "9746", "taxon": "Mus musculus", "title": "Transcriptional Profiling of Diabetic Neuropathy in BKS-db/db Mouse, a Model for Type 2 Diabetes", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34122109:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c8532a0a37032f2c6dd5cf1c71ccd8181ee0bf1b3573e642541b61627fe4c21c", "bytes": 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"0.005947408", "PRPH, NEFH, NEFL, NEFM"], ["KEGG_PATHWAY", "mmu04721:Synaptic vesicle cycle", "4", "0.010210301", "SLC17A7, SLC17A6, CPLX1, ATP6V1G2"], ["KEGG_PATHWAY", "mmu04080:Neuroactive ligand-receptor interaction", "7", "0.016857166", "GABRG1, F2RL2, ADRB3, GABRG2, AGTR1B, GRM7, NPY2R"], ["Upregulated", "KEGG_PATHWAY", "mmu04115:p53 signaling pathway", "4", "0.00976751", "CCNB1, CDK1, CCNB2, SERPINE1"], ["KEGG_PATHWAY", "mmu04610:Complement and coagulation cascades", "4", "0.013749751", "C6, SERPINE1, F7, CFI"], ["KEGG_PATHWAY", "mmu04914:Progesterone-mediated oocyte maturation", "4", "0.019706172", "CCNB1, CDK1, CCNB2, BUB1"], ["KEGG_PATHWAY", "mmu04114:Oocyte meiosis", "4", "0.037781539", "CCNB1, CDK1, CCNB2, BUB1"], ["KEGG_PATHWAY", "mmu04080:Neuroactive ligand-receptor interaction", "6", "0.039529327", "GABRR2, AGTR2, MC2R, OXTR, TSHR, CHRNA2"], ["KEGG_PATHWAY", "mmu04110:Cell cycle", "4", "0.048667279", "CCNB1, CDK1, CCNB2, BUB1"]], "row_count": 13, "column_count": 6, 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["KEGG_PATHWAY", "mmu04721:Synaptic vesicle cycle", "4", "0.010210301", "SLC17A7, SLC17A6, CPLX1, ATP6V1G2"], ["KEGG_PATHWAY", "mmu04080:Neuroactive ligand-receptor interaction", "7", "0.016857166", "GABRG1, F2RL2, ADRB3, GABRG2, AGTR1B, GRM7, NPY2R"], ["Upregulated", "KEGG_PATHWAY", "mmu04115:p53 signaling pathway", "4", "0.00976751", "CCNB1, CDK1, CCNB2, SERPINE1"], ["KEGG_PATHWAY", "mmu04610:Complement and coagulation cascades", "4", "0.013749751", "C6, SERPINE1, F7, CFI"], ["KEGG_PATHWAY", "mmu04914:Progesterone-mediated oocyte maturation", "4", "0.019706172", "CCNB1, CDK1, CCNB2, BUB1"], ["KEGG_PATHWAY", "mmu04114:Oocyte meiosis", "4", "0.037781539", "CCNB1, CDK1, CCNB2, BUB1"], ["KEGG_PATHWAY", "mmu04080:Neuroactive ligand-receptor interaction", "6", "0.039529327", "GABRR2, AGTR2, MC2R, OXTR, TSHR, CHRNA2"], ["KEGG_PATHWAY", "mmu04110:Cell cycle", "4", "0.048667279", "CCNB1, CDK1, CCNB2, BUB1"]], "row_count": 13, "column_count": 6, "numeric_cells": 40, "header_rows": 1, 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"caption": "Reanalysis hub genes via KEGG pathway enrichment analysis.", "rows": [["Category", "Term", "Count", "p-Value", "Genes"], ["KEGG_PATHWAY", "cfa04914:Progesterone-mediated oocyte maturation", "4", "7.92E-06", "CCNB1, CDK1, CCNB2, BUB1"], ["KEGG_PATHWAY", "cfa04110:Cell cycle", "4", "2.33E-05", "CCNB1, CDK1, CCNB2, BUB1"], ["KEGG_PATHWAY", "cfa04115:p53 signaling pathway", "3", "5.41E-04", "CCNB1, CDK1, CCNB2"], ["KEGG_PATHWAY", "cfa04114:Oocyte meiosis", "3", "1.49E-03", "CDK1, CCNB2, BUB1"]], "row_count": 5, "column_count": 5, "numeric_cells": 12, "header_rows": 1, "locator": "section[18]/table-wrap[1]#T5"}}, {"id": "asset:table:pmid:34122109:9", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f766afca467419cd9103b647e6a8170d240aebdcf9ad0bebaded15870b31dbb5", "bytes": 792, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": 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