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.
化疗药物紫杉醇可导致高达68%的癌症患者出现周围神经病变，这是一种剂量限制性副作用。本研究基于先前在斑马鱼和啮齿动物中的发现，探讨了紫杉醇治疗对伴有化疗诱导性周围神经病变（CIPN）的乳腺癌患者皮肤的影响。通过包括神经学检查和生活质量问卷在内的综合评估，随后采用皮肤穿刺活检进行表皮内神经纤维（IENF）密度评估。此外，RNA测序、基质金属蛋白酶13（MMP-13）免疫染色及透射电子显微镜分析揭示了该皮肤组织的分子和超微结构变化。结果显示，尽管患者报告存在CIPN症状，但对照组与CIPN患者的IENF密度无显著差异。然而，皮肤组织的RNA测序和免疫染色显示MMP-13显著上调，已知该因子在紫杉醇治疗引起的CIPN中起关键作用。此外，参与细胞外基质、微管、细胞周期和神经系统调控的多种基因均呈现显著差异表达。皮肤超微结构检查显示胶原蛋白和基底膜结构发生变化。这些发现表明，在IENF密度未发生改变的情况下仍存在CIPN，并支持皮肤重塑作为CIPN主要促成因素的作用。
肿瘤(癌症)患者之家