结直肠癌患者粪便中短链脂肪酸特征分析_张斌.pdf

临床医学研究与实践2023 年 3 月第 8 卷第 7 期研究原著Analysis of characteristics of short-chain fatty acids in feces of patients withcolorectal cancerZHANG Bin,WEN Bo,LIU Zhenggang,CHEN Dairu,YU Yuanyou,LI Sheng*(Shaoyang Hospital Affiliated to University of South China,Shaoyang 422000,China)ABSTRACT:Objective To analyze the characteristics of short-chain fatty acids(SCFAs)in feces of patients withcolorectal cancer(CRC),and provide useful information for early screening and treatment of the disease.Methods FromJanuary to July 2022,44 CRC patients(20 cases of right colon cancer,24 cases of left colon cancer),42 cases of colonadenomatous polyps(CAP)admitted in gastrointestinal surgery department and 40 healthy people in physical examinationcenter of Shaoyang Hospital Affiliated to University of South China were selected and divided into CRC group,CAP groupand HP group.The concentration of SCFAs in feces was determined by gas chromatography-mass spectrometry(GC-MS).The GC-MS detection results was record;the concentration of SCFAs in feces of the three groups was compared;theconcentration of SCFAs in feces of patients with right colon cancer and left colon cancer was compared;partial leastsquares discriminant analysis(PLS-DA)was used to determine the characteristics of SCFAs in feces of each group.ResultsSix SCFAs had good linear relationship within their respective linear range(R20.9998).Compared with the HP group,theconcentration of acetic acid,propionic acid,butyric acid and total SCFAs in feces of the CRC group decreased,while theconcentration of isovaleric acid increased,and the differences were statistically significant(P0.05);compared with the CAPgroup,the concentration of butyric acid in feces of the CRC group decreased,and the difference was statistically significant(P0.05).Theconcentration of acetic acid and total SCFAs in feces of patients with right colon cancer was higher than that of patientswith left colon cancer,and the differences were statistically significant(P0.05).The PLS-DA model showed that theseparation between CRC patients and healthy people was obvious,while the CAP patients were located between CRCpatients and healthy people.The model did not over-fit,combined with the variable importance in projection(VIP),it wasfound that acetic acid,propionic acid and butyric acid could be used as potential diagnostic markers of CRC.ConclusionThe concentration of SCFAs in feces of CAP patients is between those of CRC patients and healthy people,which to acertain extent indicates that CRC occurs on the basis of changes in the intestinal environment.The concentration of totalSCFAs in feces of CRC patients is significantly lower than that of healthy people,especially acetic acid,propionic acid and结直肠癌患者粪便中短链脂肪酸特征分析张斌，文波，刘正刚，陈代儒，喻远尤，李胜*（南华大学附属邵阳医院，湖南 邵阳，422000）摘要：目的 分析结直肠癌（CRC）患者粪便中短链脂肪酸（SCFAs）特征，为疾病的早筛和治疗提供有用信息。方法 选取2022 年 1 月至 7 月南华大学附属邵阳医院胃肠外科收治的 44 例 CRC 患者（右半结肠癌 20 例，左半结肠癌 24 例）、42 例结肠腺瘤性息肉（CAP）患者及体检中心 40 名健康人群，依次设为 CRC 组、CAP 组、HP 组。采用气相色谱-质谱联用法（GC-MS）测定粪便中 SCFAs 浓度。记录 GC-MS 检测结果；比较三组粪便中 SCFAs 浓度；比较右半结肠癌和左半结肠癌患者粪便中 SCFAs 浓度；采用偏最小二乘判别分析（PLS-DA）确定各组粪便中 SCFAs 特征。结果 6 种 SCFAs 在各自的线性范围内线性关系良好（R20.9998）。与 HP 组比较，CRC 组粪便中乙酸、丙酸、丁酸浓度及总 SCFAs 浓度降低，异戊酸浓度升高，差异具有统计学意义（P0.05）；与 CAP 组比较，CRC 组粪便中丁酸浓度降低，差异具有统计学意义（P0.05）。CAP 组与 HP 组粪便中乙酸、丙酸、异丁酸、丁酸、异戊酸、戊酸浓度及总 SCFAs 浓度比较，差异无统计学意义（P0.05）。右半结肠癌患者粪便中乙酸浓度及总 SCFAs 浓度高于左半结肠癌患者，差异具有统计学意义（P0.05）。从PLS-DA 模型可以看出 CRC 患者与健康人群分离较明显，而 CAP 患者位于 CRC 患者与健康人群之间，该模型未过度拟合，结合变量投影重要性（VIP）发现，乙酸、丙酸、丁酸可作为 CRC 潜在的诊断标志物。结论 CAP 患者粪便中 SCFAs浓度介于 CRC 患者与健康人群之间，在一定程度上说明 CRC 是在肠道环境改变的基础上发生的。CRC 患者粪便中总SCFAs 浓度较健康人群明显降低，特别是乙酸、丙酸、丁酸可作为 CRC 早期筛查的潜在标志物。关键词：结直肠癌；结肠腺瘤性息肉；短链脂肪酸；气相色谱-质谱联用法中图分类号：R735.3文献标志码：A文章编号：2096-1413(2023)07-0001-05DOI:10.19347/ki.2096-1413.202307001基金项目：邵阳市科技计划项目（No.2021072ZD）。作者简介：张斌（1993），男，硕士在读。研究方向：结直肠癌。*通讯作者：李胜，E-mail:.1-临床医学研究与实践2023 年 3 月第 8 卷第 7 期表 1三组的一般资料比较组别例数年龄（x?s，岁）性别（男/女，n）CRC 组4464.9511.5122/22CAP 组4262.989.7624/18HP 组4063.759.3120/20F0.4060.573P0.6670.751butyric acid can be used as potential markers for early screening of CRC.KEYWORDS:colorectal cancer;colon adenomatous polyps;short-chain fatty acids;gas chromatography-mass spectrometry据世界卫生组织癌症研究中心的 GLOBOCAN 项目表明，2020 年全球范围内结直肠癌（colorectal cancer,CRC）新发病例将超过 190 万，死亡人数约为 93.5 万，约占十分之一的癌症病例和死亡病例1。由于该病的早期病变多表现为亚临床症状，因此，许多 CRC 患者因诊治的延误而导致生存期的缩短2。所以早期发现、早期诊断、早期治疗对降低 CRC 的发病率及死亡率十分重要。CRC 的发生是一个异质的过程，饮食、环境和微生物暴露以及宿主免疫都会对其产生影响3。随着近年来对代谢组学及癌症表观遗传学研究的深入，越来越多的证据指向肠道菌群失调是诱发 CRC 的关键因素4。短链脂肪酸（short-chain fatty acids,SCFAs）作为肠道菌群发酵膳食纤维的最终产物，对于维持肠道菌群稳态至关重要5。SCFAs的抗炎、抗肿瘤观点也早已得到充分证明6。目前用于检测粪便中 SCFAs 浓度的方法很多，如高效液相色谱、质谱、电化学检测、气相色谱、核磁共振等7。本研究基于 SCFAs 的化学性质（易挥发性）、仪器的可重复性和稳定性，采用气相色谱-质谱联用法（gas chromatography-mass spectrometry,GC-MS）测定 CRC、结肠腺瘤性息肉（colon adenomatous polyps,CAP）患者及健康人群粪便中SCFAs 丰度，并通过内标法定量计算 SCFAs 浓度，以确定CRC、CAP患者及健康人群粪便中SCFAs水平的差异，为CRC的早筛和治疗提供有用的信息，现将具体内容报道如下。1资料与方法1.1 一般资料选取 2022 年 1 月至 7 月南华大学附属邵阳医院胃肠外科收治的 44 例 CRC 患者、42 例 CAP 患者（均已完成肠镜活检并确诊为 CRC 或 CAP）及体检中心 40 名健康人群，依次设为 CRC 组、CAP 组、HP 组。三组的年龄、性别无显著差异（P0.05，表1）。CRC组的身体质量指数（bodymassindex,BMI）为（2