| アブストラクト | Taxane drugs are essential chemotherapeutic agents in the clinical management of various solid tumors; however, their associated psychiatric adverse effects and underlying mechanisms remain insufficiently explored. This study aims to assess the association between taxane drugs and psychiatric adverse events (pAEs) and to investigate their potential biological mechanisms. The association between taxane drugs and pAEs was analyzed using the reporting odds ratio (ROR) method based on data from the Food and Drug Administration Adverse Event Reporting System (FAERS) (2013-2023) and the World Health Organization's global pharmacovigilance database (Vigibase database). Tumor-bearing mouse models treated with taxane drugs were developed, and RNA sequencing was conducted to examine the underlying molecular mechanisms. Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate the activity of relevant pathways. A total of 10,132 cases and 10,525 cases of pAEs associated with taxane drugs were identified in the FAERS and Vigibase databases, respectively. Nine significant taxane-related psychiatric adverse events (TX-related pAEs) were identified, with emotional distress showing the strongest signal. Subgroup analysis indicated that women (ROR(FAERS) = 15.244), individuals younger than 45 years (ROR(FAERS) = 17.849), and breast cancer patients exhibited a higher risk. Mechanistic studies revealed four significantly associated signaling pathways: cobalamin metabolic process, regulation of response to oxidative stress, G protein-coupled receptor signaling, and nitric oxide-mediated signal transduction. This study is the first to systematically assess taxane drug-associated pAEs, elucidating the characteristics of high-risk populations and underlying molecular mechanisms, thereby offering valuable insights for clinical drug safety and personalized treatment. |
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| 投稿者 | Lin, Anqi; Mai, Yiyin; Lai, Guichuan; Li, Zhengrui; Shen, Junyi; Wong, Hank Z H; Zhang, Nan; Zhang, Jian; Li, Kailai; Cheng, Quan; Ye, Bicheng; Jiang, Aimin; Luo, Peng; Jia, Guiqing; Chen, Qunqing |
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| 組織名 | Department of Oncology, Zhujiang Hospital, Southern Medical University,;Guangzhou, 510282, China.;Donghai County People's Hospital (Affiliated Kangda College of Nanjing Medical;University), Lianyungang, 222000, China.;Department of Health Statistics, School of Public Health, Chongqing Medical;University, Chongqing, 401331, China.;Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's;Hospital, College of Stomatology, Shanghai Jiao Tong University School of;Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key;Laboratory of Stomatology and Shanghai Research Institute of Stomatology,;Shanghai, 200011, China.;Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR,;China.;College of Life Science and Technology, Huazhong University of Science and;Technology, Wuhan, China.;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha,;410008, China.;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital,;Central South University, Changsha, 410008, China.;Liver Disease Center of Integrated Traditional Chinese and Western Medicine,;Department of Radiology, Zhongda Hospital, Medical School, Southeast University,;Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging &;Interventional Radiology (Southeast University), Nanjing, China.;Department of Urology, Changhai Hospital, Naval Medical University (Second;Military Medical University), Shanghai, 200433, China. czjiangaimin@smmu.edu.cn.;Guangzhou, 510282, China. luopeng@smu.edu.cn.;University), Lianyungang, 222000, China. luopeng@smu.edu.cn.;Department of Gastrointestinal Surgery, Sichuan Provincial People's Hospital,;University of Electronic Science and Technology of China, Chengdu, China.;jiaguiqing@med.uestc.edu.cn.;Department of Cardiothoracic Surgery, Zhujiang Hospital, Southern Medical;University, Guangzhou, China. chenqqg1985@sina.com. |
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