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肠道微生物群介导的核苷酸合成削弱直肠癌新辅助化疗的反应
2022-12-24 11:02

北京大学詹启敏等研究人员合作发现,肠道微生物群介导的核苷酸合成削弱直肠癌新辅助化疗的反应。2022年12月22日,《癌细胞》杂志在线发表了这项成果。

研究人员对353份粪便标本进行了16S rRNA测序,发现新辅助化疗(nCRT)后微生物多样性减少。多组学数据整合显示,硫化细菌介导的核苷酸生物合成与局部晚期直肠癌(LARC)患者的nCRT抗性有关,无反应的肿瘤的特点是与DNA修复和核苷酸运输有关的基因上调。核苷补充剂或B. vulgatus灌胃可保护癌细胞免受5-氟尿嘧啶或辐照治疗。对735名患者的2205份血清样本分析表明,尿酸是接受nCRT的LARC患者的潜在预后标志物。
 
这些数据揭示了肠道微生物群介导的核苷酸生物合成在直肠肿瘤对nCRT反应中的作用,并强调了在癌症治疗过程中破译癌细胞和肠道微生物之间交流的重要性。
 
据了解,术前nCRT是LARC患者的标准治疗方法,但对患者异质性反应的介导因素知之甚少。
 
附:英文原文

Title: Gut microbiota-mediated nucleotide synthesis attenuates the response to neoadjuvant chemoradiotherapy in rectal cancer

Author: Huajing Teng, Yan Wang, Xin Sui, Jiawen Fan, Shuai Li, Xiao Lei, Chen Shi, Wei Sun, Maxiaowei Song, Hongzhi Wang, Dezuo Dong, Jianhao Geng, Yangzi Zhang, Xianggao Zhu, Yong Cai, Yongheng Li, Bo Li, Qingjie Min, Weihu Wang, Qimin Zhan

Issue&Volume: 2022-12-22

Abstract: Preoperative neoadjuvant chemoradiotherapy (nCRT) is a standard treatment for locally advanced rectal cancer (LARC) patients, yet little is known about the mediators underlying the heterogeneous patient response. In this longitudinal study, we performed 16S rRNA sequencing on 353 fecal specimens and find reduced microbial diversity after nCRT. Multi-omics data integration reveals that Bacteroides vulgatus-mediated nucleotide biosynthesis associates with nCRT resistance in LARC patients, and nonresponsive tumors are characterized by the upregulation of genes related to DNA repair and nucleoside transport. Nucleosides supplementation or B. vulgatus gavage protects cancer cells from the 5-fluorouracil or irradiation treatment. An analysis of 2,205 serum samples from 735 patients suggests that uric acid is a potential prognosis marker for LARC patients receiving nCRT. Our data unravel the role of intestinal microbiota-mediated nucleotide biosynthesis in the response of rectal tumors to nCRT, and highlight the importance of deciphering the cross-talk between cancer cells and gut microorganisms during cancer therapies.

DOI: 10.1016/j.ccell.2022.11.013

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00560-8

 

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:38.585
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx


本期文章:《癌细胞》:Online/在线发表

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