New Metabolic Alterations and A Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma  

作　　者：Lei Liu Jia Wu Minxin Shi Fengying Wang Haimin Lu Jibing Liu Weiqin Chen Guanzhen Yu Dan Liu Jing Yang Qin Luo Yan Ni Xing Jin Xiaoxia Jin Wen-Lian Chen 

机构地区：[1]Department of Thoracic Surgery,The Affiliated Tumor Hospital of Nantong University,Nantong 226361,China [2]Cancer Institute,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China [3]Department of Epidemiology,Tumor Institute,The Affiliated Tumor Hospital of Nantong University,Nantong 226361,China [4]Department of Clinical Laboratory,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China [5]The Children’s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310029,China [6]Department of Pathology,The Affiliated Tumor Hospital of Nantong University,Nantong 226361,China

出　　处：《Genomics, Proteomics & Bioinformatics》2022年第4期670-687,共18页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.31970708,81770147,81802891,and 82002953);the National Scientific and Technological Major Special Project of China(Grant No.2019ZX09201004-002-013);the National Thirteenth Five-Year Science and Technology Major Special Project for New Drug Innovation and Development(Grant No.2017ZX09304001);the Research fund of Shanghai Municipal Commission of Health(Grant No.20174Y0090);the Shanghai Rising-Star Program(Grant No.18QA1404100);the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning;the Shanghai Youth Talent Program;the Shanghai Municipal Key Clinical Specialty(Grant No.shslczdzk03701);the Three-Year Plan of Shanghai Municipality for Further Accelerating The Development of Traditional Chinese Medicine[Grant No.ZY(20182020)-CCCX-1016];the Shanghai Chenguang Program(Grant No.18CG47);the grant from Nantong Tumor Hospital(Grant No.BS201909);the Gaofeng Clinical Medicine Grant of Shanghai Municipal Education Commission;the Health Commission of Pudong New Area Health and Family Planning Scientific Research Project(Grant No.PW2019E-1);the Xinling Scholar Program of Shanghai University of Traditional Chinese Medicine,China。

摘　　要：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.

关 键 词：Esophageal squamous cell carcinoma Serum metabolome ESOPHAGECTOMY Predictive potential Pipecolic acid 

分 类 号：R735.1[医药卫生—肿瘤]