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pmid:38716040
Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis.
Yaling Lou · Xuting Xu · Ronghua Wang · Danfeng Yao
Journal of pain research · 2024 doi:10.2147/JPR.S452594
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Experiment
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Complete file
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This study was aimed to uncover the key genes as well as protein networks that contribute to Oxaliplatin-induced NP.\nMaterial/Methods: Oxaliplatin frequently results in a type of Chemotherapy-induced NP that is marked by heightened sensitivity to mechanical and cold stimuli, which can lead to intolerance and discontinuation of medication. We investigated whether these different etiologies lead to similar pathological outcomes by targeting shared genetic targets or signaling pathways. Gene expression data were obtained from the Gene Expression Comprehensive Database (GEO) for GSE38038 (representing differential expression in the spinal nerve ligation model rats) and GSE126773 (representing differential expression among the Oxaliplatin-induced NP model rats). Differential gene expression analysis was performed using GEO2R.\nResults: Protein-protein interaction (PPI) analysis identified 260 co-differentially expressed genes (co-DEGs). Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed three shared pathways involved in both models: Kaposi sarcoma-associated herpesvirus (KSHV) infection, Epstein-Barr virus (EBV) infection, and AGE-RAGE signaling pathway in diabetic complications. Further bioinformatics analysis highlighted eight significantly up-regulated genes in the NP group: Mapk14, Icam1, Cd44, IL6, Cxcr4, Stat1, Casp3 and Fgf2. Our results suggest that immune dysfunction, inflammation-related factors or regulating inflammation factors may also be related to Oxaliplatin-induced NP. Additionally, we analyzed a dataset (GSE145222) involving chronic compression of DRGs (CCD) and control groups. CCD model is a classic model for studying NP. We assessed these hub genes' expression levels. In contrast with the control groups, the hub genes were up-regulated in CCD groups, the difference was statistically significant, except Stat1.\nConclusion: Our research significantly contributes to elucidating the mechanisms underlying the occurrence as well as the progression of Oxaliplatin-induced NP. We have identified crucial genes and signaling pathways associated with this condition.", "claims": [{"id": "claim-method", "statement": "To differentiate DEGs of the diseased and control groups, we utilized the online analysis tool of GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r)10 on a basis of the R packages of GEOquery as well as Limma, which facilitate data reading and differential expression calculation, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38716040", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "To differentiate DEGs of the diseased and control groups, we utilized the online analysis tool of GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r)10 on a basis of the R packages of GEOquery as well as Limma, which facilitate data reading and differential expression calculation, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi; GEO accession: GSE38038; GSE126773).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38716040", "locator": "sections[18] \"Data Sharing Statement\" paragraph 2", "quote": "The data that support the findings of this study are downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi; GEO accession: GSE38038; GSE126773)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Comparative bioinformatics analysis of oxaliplatin-induced and spinal nerve ligation-induced neuropathic pain identified 260 common differentially expressed genes, shared pathways, and eight upregulated candidate hub genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38716040", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Protein-protein interaction (PPI) analysis identified 260 co-differentially expressed genes (co-DEGs)."}, {"asset": "source:pmid:38716040", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Further bioinformatics analysis highlighted eight significantly up-regulated genes in the NP group: Mapk14, Icam1, Cd44, IL6, Cxcr4, Stat1, Casp3 and Fgf2."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Comparative bioinformatics analysis of oxaliplatin-induced and spinal nerve ligation-induced neuropathic pain identified 260 common differentially expressed genes, shared pathways, and eight upregulated candidate hub genes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38716040"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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