Chemotherapy‐induced peripheral neuropathy (CIPN) is among the most disabling and frustrating problems for cancer survivors. The neurotoxicity caused by cisplatin varies greatly among patients, and few predictors of appearance, duration of symptoms, susceptibility, or severity are available. A deeper understanding of the mechanisms underlying individual differences in status, severity, or sensitivity in response to cisplatin treatment is therefore required. By analyzing the GSE64174 gene expression profile and constructing a weighted gene co‐expression network analysis (WGCNA) network, we screened gene modules and hub genes related to CIPN status, severity and sensitivity. We first identified the transcriptome profile of mouse dorsal root ganglion (DRG) samples and transformed their genes to human DRG counterparts. We then constructed WGCNA gene modules via optimal soft‐threshold power‐identification and module‐preservation analysis. Comprehensive analysis and identification of module hub genes were performed via functional‐enrichment analysis and significant common hub genes were identified, including “Cytoscape_cytoHubba,” “Cytoscape_MCODE,” and “Metascape_MCODE.” Brown, green, and blue modules were selected to represent CIPN sensitivity, status, and severity, respectively, via trait‐module correlational analysis. Additionally, functional enrichment analysis results indicated that these three modules were associated with some crucial biological functions, such as neutrophil migration, chemokine‐mediated signaling pathway, and PI3K‐Akt signaling pathway. We then identified seven common hub genes via three methods, including CXCL10, CCL21, CCR2, CXCR4, TLR4, NPY1R, and GALR2, related to CIPN status, severity and sensitivity. Our results provide possible targets and mechanism insights into the development and progress of CIPN, which can guide further transformation and pre‐clinical research.

中文翻译：

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根据敏感性、状态和严重程度，参与顺铂诱导的周围神经病变的共表达基因模块。

化疗引起的周围神经病变 (CIPN) 是癌症幸存者最致残和最令人沮丧的问题之一。顺铂引起的神经毒性因患者而异，几乎没有外观、症状持续时间、易感性或严重程度的预测因子。因此，需要更深入地了解个体状态、严重程度或对顺铂治疗的敏感性差异背后的机制。通过分析 GSE64174 基因表达谱并构建加权基因共表达网络分析 (WGCNA) 网络，我们筛选了与 CIPN 状态、严重程度和敏感性相关的基因模块和枢纽基因。我们首先确定了小鼠背根神经节 (DRG) 样本的转录组谱，并将其基因转化为人类 DRG 对应物。然后，我们通过最佳软阈值功率识别和模块保存分析构建 WGCNA 基因模块。通过功能富集分析对模块中枢基因进行综合分析和鉴定，并鉴定出重要的常见中枢基因，包括“Cytoscape_cytoHubba”、“Cytoscape_MCODE”和“Metascape_MCODE”。通过特质模块相关分析，选择棕色、绿色和蓝色模块分别代表 CIPN 敏感性、状态和严重程度。此外，功能富集分析结果表明，这三个模块与一些关键的生物学功能有关，如中性粒细胞迁移、趋化因子介导的信号通路和 PI3K-Akt 信号通路。然后我们通过三种方法确定了七个常见的枢纽基因，包括 CXCL10、CCL21、CCR2、CXCR4、TLR4、NPY1R 和 GALR2，与 CIPN 状态、严重程度和敏感性有关。我们的研究结果为CIPN的发展和进步提供了可能的靶点和机制见解，可以指导进一步的转化和临床前研究。