Zhuang Juntao, Yang Xiao, Zheng Qi, Li Kai, Cai Lingkai, Yu Hao, Lv Jiancheng, Bai Kexin, Cao Qiang, Li Pengchao, Yang Haiwei, Wang Junsong, Lu Qiang
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Center of Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China.
Metabolites. 2022 Jun 17;12(6):558. doi: 10.3390/metabo12060558.
Numerous patients with muscle-invasive bladder cancer develop low responsiveness to cisplatin. Our purpose was to explore differential metabolites derived from serum in bladder cancer patients treated with neoadjuvant chemotherapy (NAC). Data of patients diagnosed with cT2-4aNxM0 was collected. Blood samples were retained prospectively before the first chemotherapy for untargeted metabolomics by H-NMR and UPLC-MS. To identify characterized metabolites, multivariate statistical analyses were applied, and the intersection of the differential metabolites discovered by the two approaches was used to identify viable biomarkers. A total of 18 patients (6 NAC-sensitive patients and 12 NAC-resistant patients) were enrolled. There were 29 metabolites detected by H-NMR and 147 metabolites identified by UPLC-MS. Multivariate statistics demonstrated that in the sensitive group, glutamine and taurine were considerably increased compared to their levels in the resistant group, while glutamate and hypoxanthine were remarkably decreased. Pathway analysis and enrichment analysis showed significant alterations in amino acid pathways, suggesting that response to chemotherapy may be related to amino acid metabolism. In addition, hallmark analysis showed that DNA repair played a regulatory role. Overall, serum metabolic profiles of NAC sensitivity are significantly different in bladder cancer patients. Glycine, hypoxanthine, taurine and glutamine may be the potential biomarkers for clinical treatment. Amino acid metabolism has potential value in enhancing drug efficacy.
许多肌层浸润性膀胱癌患者对顺铂产生低反应性。我们的目的是探索接受新辅助化疗（NAC）的膀胱癌患者血清中的差异代谢物。收集了诊断为cT2 - 4aNxM0患者的数据。在首次化疗前前瞻性地保留血样，用于通过氢核磁共振（H-NMR）和超高效液相色谱-质谱联用（UPLC-MS）进行非靶向代谢组学分析。为了鉴定特征性代谢物，应用了多变量统计分析，并使用两种方法发现的差异代谢物的交集来鉴定可行的生物标志物。共纳入18例患者（6例对NAC敏感患者和12例对NAC耐药患者）。通过H-NMR检测到29种代谢物，通过UPLC-MS鉴定出147种代谢物。多变量统计表明，在敏感组中，谷氨酰胺和牛磺酸的水平与耐药组相比显著升高，而谷氨酸和次黄嘌呤则显著降低。通路分析和富集分析显示氨基酸通路有显著改变，表明对化疗的反应可能与氨基酸代谢有关。此外，特征分析表明DNA修复起调节作用。总体而言，膀胱癌患者中NAC敏感性的血清代谢谱有显著差异。甘氨酸、次黄嘌呤、牛磺酸和谷氨酰胺可能是临床治疗的潜在生物标志物。氨基酸代谢在提高药物疗效方面具有潜在价值。
