中文摘要：

目的联合质子核磁共振谱（1H-NMR）和模式识别筛寻大肠癌高危预警、早期诊断的粪便代谢标志物组。方法于2014年1—12月，在汕头大学医学院第二附属医院进行手术治疗的所有肠腺瘤和Ⅰ/Ⅱ期大肠癌病例中，选取经组织病理学确诊、治疗前未进行放疗或化疗、未使用抗生素、无上消化道及小肠病史和体征者为研究对象，肠腺瘤和Ⅰ/Ⅱ期大肠癌病例分别为25和20例。另选取来自同期本院健康体检个体，纳入无肿瘤病史、各项体检指标正常、未使用抗生素者为对照组，共32名。收集研究对象粪便样本约5-10 g，采用400 MHz 1H-NMR检测样本上清液代谢物，所得数据采用正交偏最小二乘法判别分析（OPLS-DA）进行模式识别，确定对照组和肠腺瘤及Ⅰ/Ⅱ期大肠癌的差异性粪便代谢物组，并且绘制受试者工作曲线（ROC），评估其在大肠癌早期筛查诊断的临床价值。结果Ⅰ/Ⅱ期大肠癌20例，男性11例，女性9例，年龄为（52±13）岁；肠腺瘤25例，男性14例，女性11例，年龄（53±11）岁；对照组32名，男性15名，女性17名，年龄为（53±14）岁。OPLS-DA可有效区分对照组和肠腺瘤及Ⅰ/Ⅱ期大肠癌组的粪便上清液代谢物：对照组粪便样本中丁酸、醋酸、丙酸、葡萄糖及谷氨酰胺含量的相对信号强度分别为23.0±6.0、45.0±11.0、26.0±7.0、37.0±7.0和4.5±2.0，肠腺瘤组为18.0±5.0、31.0±11.0、22.0±6.0、31.0±7.0和4.9±1.0，Ⅰ/Ⅱ期大肠癌组为14.0±6.0、24.0±8.0、19.0±5.0、26.0±8.0和5.4±1.0，均低于对照组（Z值分别为-2.07、-2.32、-2.43、-2.07和2.21，P值分别为0.008、0.011、0.032、0.044和0.044）；对照组粪便样本中乳酸、谷氨酸及琥珀酸盐含量的相对信号强度为4.8± 1.0、3.2±2.0和12.0±2.0，肠腺瘤组为6.9±2.0、4.9±1.0和15.0±3.0，Ⅰ/Ⅱ期大肠癌组为7.8±1.0、5.4±1.0和18.0±2.0，均高于对照组（Z值分别为2.02?

英文摘要：

Objective To characterize the metabolic ＂ fingerprint＂ of fecal extracts for diagnosis of early-stage colorectal cancer（CRC）using proton nuclear magnetic resonance spectroscopy（1H-NMR）-based metabolomics coupled with pattern recognition.Methods From January 2014 to December 2014, we collected fecal samples at the Second Affiliated Hospital of Shantou University Medical College, from 25 patients with colorectal adenomas（CR-Ad）, 20 with stage Ⅰ/Ⅱ CRC, and 32 healthy controls（HCs）. The patients were diagnosed by histopathology. No subjects had any complicating diseases. HCs showed no abnormalities from blood tests, endoscopic examination, diagnostic imaging, and/or medical interviews. We excluded participants who used antibiotics, NSAIDS, statins, or probiotics within two months of study participation, and any patients who underwent chemotherapy or radiation treatments prior to surgery. We used orthogonal partial least-squares-discriminant analysis（OPLS-DA）for pattern recognition（dimension reduction）on 1H-NMR processed data（1H frequency of 400.13 MHz）, to find metabolic differences among CR-Ad, carcinoma and HC fecal samples; and receiver operating characteristic（ROC）analysis to determine the diagnostic value of the fecal metabolic biomarkers.Results Fecal samples were collected from 20 patients with Stage Ⅰ/Ⅱ CRC（11 M, 9 F, median age（52±13）years）, 25 with CR-Ad（14 M, 11 F, median age（53 ± 11）years）and 32 HCs（15 M, 17 F, median age（53 ± 14）years）. OPLS-DA clearly distinguished CR-Ad and stage Ⅰ/Ⅱ CRC from HC samples, based on their metabolomic profiles. Relative signal intensities in HCs were significantly lower than in the cancer patients for butyrate（HC： 23.0±6.0; CR-Ad： 18.0±5.0; CRC： 14.0±6.0; Z=-2.07, P=0.008）, acetate（HC： 45.0±11.0; CR-Ad： 31.0±11.0; CRC： 24.0±8.0; Z=- 2.32, P=0.011）, propionate（HC： 26.0 ± 7.0; CR-Ad： 22.0 ± 6.0; CRC： 19.0 ± 5.0; Z=- 2.43, P=0.032）, glucose（HC： 37.0±7.0; C