机构：[1]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Disease, Yunan Geiatric Medical Center, Kunming, Yunnan, China 内科科室消化内科昆明医科大学附属第一医院[2]Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China 深圳市康宁医院深圳医学信息中心[3]Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China [4]Biotree Metabolomics Technology Research Center, Shanghai, China [5]Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China 浙江省肿瘤医院[6]Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 中山大学附属第一医院[7]Department of Gastrointestinal Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China [8]Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of 1,251 individuals (422 CRC, 399 colorectal adenoma [CRA], and 430 normal controls [NC]). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to a-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848-0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.
基金：
National Key R&D Program of China [2020YFA0509200/2020YFA0509203]; RGC Collaborative Research Fund [C4039-19GF, C4008-23W]; RGC Research Impact Fund [R4032-21F]; National Natural Science Foundation of China [81973127, 82060107, 82170550]; Kingboard Precision Oncology Program CUHK; CUHK Research Startup Fund [FPU/2023/149]; Major science and technology special plan of Yunnan Province [202302AA310025]; Applied Basic Research Projects of Yunnan Province, China [202201AW070019]; The "Xingdian Talents"Support Project of Yunnan Province [RLQB20220006]; Basic Research Projects of Yunan Province [202301AS070027]; Outstanding Youth Fund of Jiangsu Natural Science Foundation [BK20230005]
第一作者机构：[1]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Disease, Yunan Geiatric Medical Center, Kunming, Yunnan, China
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通讯作者：
推荐引用方式(GB/T 7714)：
Sun Yang,Zhang Xiang,Hang Dong,et al.Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers[J].CANCER CELL.2024,42(8):doi:10.1016/j.ccell.2024.07.005.
APA：
Sun, Yang,Zhang, Xiang,Hang, Dong,Lau, Harry Cheuk-Hay,Du, Jie...&Yu, Jun.(2024).Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers.CANCER CELL,42,(8)
MLA：
Sun, Yang,et al."Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers".CANCER CELL 42..8(2024)
医学