New Metabolic Alterations and A Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma.
New Metabolic Alterations and A Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma.
复制标题
DOI：
10.1016/j.gpb.2021.08.016
复制
发表时间：
2022-08
影响因子：
9.5
通讯作者：
Chen, Wen-Lian
中科院分区：
文献类型：
--
作者：
Liu, Lei;Wu, Jia;Shi, Minxin;Wang, Fengying;Lu, Haimin;Liu, Jibing;Chen, Weiqin;Yu, Guanzhen;Liu, Dan;Yang, Jing;Luo, Qin;Ni, Yan;Jin, Xing;Jin, Xiaoxia;Chen, Wen-Lian
关键词：
食管鳞状细胞癌(ESCC)是食道癌的主要组织学亚型，预后不良。尽管已有多项血清代谢组学研究报道，但ESCC肿瘤相关代谢改变和血清中的预测生物标记物尚未被定义。在这里，我们招募了34名未接受治疗的食管鳞癌患者，并收集了他们在食道切除前后的血清以及34名健康志愿者的血清进行代谢组学调查。我们的综合分析确认了由12种血清代谢物所代表的食管癌肿瘤相关的代谢改变。值得注意的是，术后禁食和肠外营养严重扰乱了血清代谢物。此外，我们使用致癌物诱导的异型增生和ESCC阶段小鼠的血清进行了检测，发现了三种在小鼠和人类之间保守的ESCC肿瘤相关代谢物。值得注意的是，在这些代谢物中，从异型增生到癌变的小鼠血清中吡哌酸的水平逐渐增加，它可以用来准确区分异型增生阶段的小鼠和健康对照组小鼠。此外，这种代谢产物对ESCC细胞抑制氧化应激诱导的DNA损伤和细胞增殖停滞是必不可少的。总而言之，这项研究揭示了一组12种与ESCC肿瘤相关的血清代谢物，它们具有监测疗效和疾病复发的潜力，为改进肠外营养成分提供了证据，并强调血清吡喃甲酸是预测ESCC肿瘤发生的一个有吸引力的生物标志物。
Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.
登录
查看更多内容
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
3.3
作者：
Liou GY;Storz P
通讯作者：
Storz P
影响因子：
7.4
作者：
Ni Y;Su M;Qiu Y;Jia W;Du X
通讯作者：
Du X
影响因子：
20.3
作者：
Chen, Wen-Lian;Wang, Jing-Han;Jia, Wei
通讯作者：
Jia, Wei
影响因子：
2.6
作者：
Gavin, A. T.;Francisci, S.;Anderson, L. A.
通讯作者：
Anderson, L. A.