Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430022, China.
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int Immunopharmacol. 2024 Oct 25;140:112728. doi: 10.1016/j.intimp.2024.112728. Epub 2024 Aug 3.
Imatinib-induced skin rash poses a significant challenge for patients with gastrointestinal stromal tumor, often resulting in treatment interruption or discontinuation and subsequent treatment failure. However, the underlying mechanism of imatinib-induced skin rashes in gastrointestinal stromal tumor patients remains unclear. A total of 51 patients (27 with rash and 24 without rash) were enrolled in our study. Blood samples were collected concomitantly with the onset of clinical manifestations of rashes, and simultaneously collecting clinical relevant information. The imatinib concentration and untargeted metabolomics were performed by ultra-high-performance liquid chromatography-tandem mass spectrometry. There were no significant differences in age, gender, imatinib concentration and white blood cells count between the rash group and the control group. However, the rash group exhibited a higher eosinophil count (P<0.05) and lower lymphocyte count (P<0.05) compared to the control group. Untargeted metabolomics analysis found that 105 metabolites were significantly differentially abundant. The univariate analysis highlighted erucamide, linoleoylcarnitine, and valine betaine as potential predictive markers (AUC≥0.80). Further enriched pathway analysis revealed primary metabolic pathways, including sphingolipid signaling pathway, sphingolipid metabolism, cysteine and methionine metabolism, biosynthesis of unsaturated fatty acids, arginine and proline metabolism, and biosynthesis of amino acids. These findings suggest that the selected differential metabolites could serve as a foundation for the prediction and management of imatinib-induced skin rash in gastrointestinal stromal tumor patients.
伊马替尼引起的皮疹对胃肠道间质瘤患者构成重大挑战，常导致治疗中断或停止，进而导致治疗失败。然而，胃肠道间质瘤患者伊马替尼引起皮疹的潜在机制尚不清楚。我们的研究共纳入了 51 名患者（27 名皮疹患者和 24 名无皮疹患者）。在皮疹出现的临床表现时同时采集血样，并同时采集临床相关信息。采用超高效液相色谱-串联质谱法进行伊马替尼浓度和非靶向代谢组学检测。皮疹组和对照组在年龄、性别、伊马替尼浓度和白细胞计数方面无显著差异。然而，皮疹组的嗜酸性粒细胞计数较高（P<0.05），淋巴细胞计数较低（P<0.05）。非靶向代谢组学分析发现 105 种代谢物存在显著差异。单变量分析突出了神经酰胺、亚油酸肉碱和缬氨酸甜菜碱作为潜在的预测标志物（AUC≥0.80）。进一步富集的途径分析显示了主要代谢途径，包括鞘脂信号通路、鞘脂代谢、半胱氨酸和蛋氨酸代谢、不饱和脂肪酸的生物合成、精氨酸和脯氨酸代谢以及氨基酸的生物合成。这些发现表明，所选差异代谢物可作为预测和管理胃肠道间质瘤患者伊马替尼引起的皮疹的基础。
