化疗药物紫杉醇可导致周围神经病变，是最多达68%癌症患者剂量限制性的副作用。本研究探讨了紫杉醇治疗对乳腺癌患者在化疗诱导的周围神经病变（CIPN）下皮肤的影响，扩展了斑马鱼和啮齿动物的先前研究发现。进行了全面评估，包括神经学检查和生活质量问卷调查，之后使用皮肤穿刺活检进行了皮肤内上皮神经纤维（IENF）密度评估。此外，RNA测序、Matrix-Metalloproteinase 13（MMP-13）的免疫染色和透射电子显微镜分析提供了有关此皮肤分子和超微结构变化的见解。结果显示，尽管存在患者报告的CIPN症状，但控制组与CIPN患者的IENF密度没有显著差异。然而，皮肤的RNA测序和免疫染色结果显示MMP-13明显上调，而MMP-13在紫杉醇治疗引起的CIPN中发挥关键作用。此外，涉及细胞外基质、微管、细胞周期和神经系统调节的各种基因的表达在CIPN患者中显著而差异地改变。皮肤的超微结构检查显示胶原和基底膜结构发生变化。这些发现突显了在缺乏IENF密度变化的情况下存在CIPN，并支持皮肤重塑作为CIPN主要贡献因素的作用。

The chemotherapeutic agent paclitaxel causes peripheral neuropathy, a dose-limiting side effect, in up to 68% of cancer patients. In this study, we investigated the impact of paclitaxel therapy on the skin of breast cancer patients with chemotherapy-induced peripheral neuropathy (CIPN), building upon previous findings in zebrafish and rodents. Comprehensive assessments, including neurological examinations and quality of life questionnaires, were conducted, followed by intraepidermal nerve fiber (IENF) density evaluations using skin punch biopsies. Additionally, RNA sequencing, immunostaining for Matrix-Metalloproteinase 13 (MMP-13), and transmission electron microscopy provided insights into molecular and ultrastructural changes in this skin. The results showed no significant difference in IENF density between the control and CIPN patients despite the presence of patient-reported CIPN symptoms. Nevertheless, the RNA sequencing and immunostaining on the skin revealed significantly upregulated MMP-13, which is known to play a key role in CIPN caused by paclitaxel therapy. Additionally, various genes involved in the regulation of the extracellular matrix, microtubules, cell cycle, and nervous system were significantly and differentially expressed. An ultrastructural examination of the skin showed changes in collagen and basement membrane structures. These findings highlight the presence of CIPN in the absence of IENF density changes and support the role of skin remodeling as a major contributor to CIPN.