Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer
Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer
复制标题
新辅助放化疗后肿瘤代谢变化可预测胰腺癌患者术后复发
DOI：
10.1093/jjco/hyac074
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发表时间：
2022
影响因子：
2.4
通讯作者：
Sog
中科院分区：
文献类型：
--
作者：
Wada Yukiko;Okano Keiichi;Sato Kiyotoshi;Sugimoto Masahiro;Shimomura Ayaka;Nagao Mina;Matsukawa Hiroyuki;Ando Yasuhisa;Suto Hironobu;Oshima Minoru;Kondo Akihiro;Asano Eisuke;Kishino Takayoshi;Kumamoto Kensuke;Kobara Hideki;Kamada Hideki;Masaki Tsutomu;Sog
目的探讨胰腺导管腺癌的代谢变化，探讨新辅助放化疗的疗效机制。方法前瞻性采集88例接受根治性手术的胰腺导管腺癌患者的冷冻肿瘤组织和非肿瘤性胰腺组织。 62 例患者接受新辅助放化疗，26 例患者未接受新辅助治疗（对照组）。采用毛细管电泳-质谱法对肿瘤和非肿瘤胰腺组织中的代谢物进行综合分析。结果毛细管电泳-质谱法在定量的500多种离子代谢物中检测到90种代谢物进行分析。新辅助放化疗组与对照组的27种肿瘤代谢物存在显着差异。新辅助放化疗反应良好者和反应差者之间的八种代谢物 [1-甲基烟酰胺、肉碱、葡萄糖、谷胱甘肽（红色）、N-乙酰氨基葡萄糖 6-磷酸、N-乙酰氨基葡萄糖 1-磷酸、UMP、磷酸胆碱] 存在显着差异。在这些代谢物中，磷酸胆碱、肉碱和谷胱甘肽仅在新辅助放化疗组中与无复发生存相关。微阵列证实新辅助放化疗组胰腺导管腺癌组织中胆碱转运蛋白[CTL1-4 (SLC44A1-44A4)]的基因受到显着抑制。结论本研究确定了胰腺导管腺癌中几个重要的代谢后果和潜在的新辅助放化疗靶点。胆碱代谢是接受新辅助放化疗的胰腺导管腺癌患者复发的关键途径之一。
ObjectiveWe investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy.MethodsFrozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry.ResultsCapillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group.ConclusionThe present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.