PMID- 38018513 OWN - NLM STAT- MEDLINE DCOM- 20240312 LR - 20240313 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 16 IP - 3 DP - 2024 Mar TI - Diagnostic biomarker for type 2 diabetic peripheral neuropathy via comprehensive bioinformatics analysis. PG - e13506 LID - 10.1111/1753-0407.13506 [doi] LID - e13506 AB - BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes mellitus (T2DM), which frequently results in disabling neuropathic pain and lower-limb amputation. The identification of noninvasive biomarkers for DPN may help early detection and individualized treatment of DPN. METHODS: In this study, we identified differentially expressed genes (DEGs) between DPN and the control based on blood-source (GSE95849) and tissue-source gene expression profiles (GSE143979) from the Gene Expression Omnibus (GEO) database using limma, edgeR, and DESeq2 approaches. KEGGG and GO functional enrichments were performed. Hub genes and their correlation with infiltrating immune cells were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify hub gene expression. RESULTS: In total, 144 DEGs between DPN and the control were identified. Functional enrichment revealed that the DEGs were mainly enriched in immune-related pathways like the Fc epsilon receptor Ig signaling pathway. By protein-protein interaction (PPI) network analysis, FCER1G, SYK, ITGA4, F13A1, MS4A2, and PTK2B were screened as hub genes with higher expression in DPN patients, among which half were immune genes (FCER1G, PTK2B, and SYK). RT-qPCR demonstrated that mRNA expression of FCER1G, PTK2B, and SYK was significantly increased in patients with DPN compared with both diabetic nonperipheral neuropathy (DNN) and normal subjects. The area under the receiver operating characteristic (ROC) curve of FCER1G, PTK2B, and SYK was 0.84, 0.81, and 0.73, respectively, suggesting their great advantages as diagnostic biomarkers to predict the progression of neuropathy in T2DM. Further analysis indicated that the expression of FCER1G, PTK2B, and SYK was negatively correlated with the cell proportion of significantly altered resting natural killer cells, T follicular helper cells, and activated mast cells, but positively correlated with monocytes. CONCLUSIONS: Our findings demonstrated FCER1G, PTK2B, and SYK are potential diagnostic biomarkers and therapeutic targets for DPN, which provides new insight into DPN pathogenesis and therapies. CI - (c) 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Chen, Xiaoyu AU - Chen X AD - Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. FAU - Liu, Qingquan AU - Liu Q AD - Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. FAU - Chen, Niyao AU - Chen N AD - Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. FAU - Ma, Jiangxin AU - Ma J AD - Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. FAU - Wu, Xiaohong AU - Wu X AD - Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. FAU - Zhang, Haibin AU - Zhang H AD - Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. FAU - Yu, Liying AU - Yu L AUID- ORCID: 0000-0002-0404-2385 AD - Central Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. FAU - Huang, Huibin AU - Huang H AD - Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China. LA - eng GR - 2019-ZQN-66/Fujian Provincial Health and Health Scientific Research Talent Training/ GR - 2020N035s/Fujian Quanzhou Science and Technology Plan/ GR - 2022J01279/Natural Science Foundation of Fujian Province/ GR - BS202203/the doctoral research project of Second Affiliated Hospital of Fujian Medical University/ GR - 2022BD0704/the doctoral research project of Second Affiliated Hospital of Fujian Medical University/ PT - Journal Article DEP - 20231129 PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/genetics MH - *Diabetic Neuropathies/etiology/genetics MH - Amputation, Surgical MH - Computational Biology MH - Databases, Factual PMC - PMC10925884 OTO - NOTNLM OT - Type 2 diabetes OT - bioinformatic analysis OT - immune gene OT - immune infiltration OT - peripheral neuropathy COIS- None declared. EDAT- 2023/11/29 06:42 MHDA- 2024/03/12 11:45 PMCR- 2023/11/29 CRDT- 2023/11/29 05:53 PHST- 2023/09/12 00:00 [revised] PHST- 2022/10/19 00:00 [received] PHST- 2023/11/08 00:00 [accepted] PHST- 2024/03/12 11:45 [medline] PHST- 2023/11/29 06:42 [pubmed] PHST- 2023/11/29 05:53 [entrez] PHST- 2023/11/29 00:00 [pmc-release] AID - JDB13506 [pii] AID - 10.1111/1753-0407.13506 [doi] PST - ppublish SO - J Diabetes. 2024 Mar;16(3):e13506. doi: 10.1111/1753-0407.13506. Epub 2023 Nov 29.