结直肠癌肝转移患者新辅助化疗效果相关的肠道菌群和代谢物特征及其临床预测价值  

Characteristics and clinical predictive value of gut microbiota and metabolites related to neoadjuvant chemotherapy effect in patients with colorectal cancer liver metastases

作　　者：张馨雅 王一凡 李金铭 张淑君 李培龙 王传新 杜鲁涛[3] Zhang Xinya;Wang Yifan;Li Jinming;Zhang Shujun;Li Peilong;Wang Chuanxin;Du Lutao(Department of Clinical Laboratory,the Second Hospital of Shandong University,Ji′nan 250033,China;Department of Colorectal Surgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China;Department of Clinical Laboratory,Qilu Hospital of Shandong University,Ji′nan 250012,China)

机构地区：[1]山东大学第二医院检验医学中心,济南250033 [2]复旦大学附属肿瘤医院大肠外科,上海200032 [3]山东大学齐鲁医院检验医学中心,济南250012

出　　处：《中华检验医学杂志》2024年第7期779-788,共10页Chinese Journal of Laboratory Medicine

基　　金：山东省重大科技创新工程项目(2021ZLGX02)。

摘　　要：目的:筛选与结直肠癌肝转移以奥沙利铂为基础的新辅助化疗患者疗效相关的特征性肠道菌群及粪便代谢物,分析肠道菌群与粪便代谢物之间的关系,评估相关标志物在结直肠癌新辅助化疗中的疗效预测价值。方法:病例对照研究。选取2021年10月—2022年7月在山东大学齐鲁医院就诊的34例结直肠癌肝转移患者为研究对象,根据疗效评价标准,分为化疗有效组(20例)和化疗无效组(14例),患者粪便样本进行宏基因组测序和非靶向代谢组学分析,获得与结直肠癌肝转移化疗疗效相关的菌群及代谢物特征,采用Logistic回归构建预测模型筛选可预测化疗效果的菌群及代谢标志物,绘制受试者工作特征(ROC)曲线以及生存分析曲线评价相关菌种和代谢物对新辅助化疗疗效的预测效果。结果:化疗有效组与无效组患者的肠道菌群的α和β多样性差异无统计学意义(P均>0.05)。在菌种方面,与化疗无效组比较,化疗有效组有5种菌种相对丰度上调,10种菌种相对丰度下调,差异有统计学意义(P均<0.05),其中唾液普雷沃菌能有效预测化疗效果(ROC曲线下面积为0.750,P=0.007),敏感度为80.0%,特异度为71.4%,且其丰度高水平患者(17例)总生存率低于丰度低水平患者(17例)(χ^(2)=5.239,P=0.022)。在代谢物方面,与化疗无效组比较,化疗有效组有20种代谢物上调,4种代谢物下调,差异有统计学意义(P均<0.05),其中苏氨酸和前列腺素F2α-1-乙醇酰胺可区分化疗有效与无效患者(AUC=0.743、0.707,P均<0.05),并且两者相对丰度高水平患者(17例)总生存率高于低水平患者(17例)(χ^(2)=4.748、5.407,P均<0.05)。通过筛选分析获得唾液普雷沃菌和前列腺素F2α-1-乙醇酰胺的Logistic回归模型,ROC曲线结果显示,该模型对患者的疗效具有较好的预测价值(AUC=0.836,P<0.05),敏感度为90.0%,特异度为78.6%,且模型预测生存概率高水平患者(17例)总生存率高于低水平�Objective To screen the characteristic gut microbiota and fecal metabolites related to the efficacy of oxaliplatin-based neoadjuvant chemotherapy in patients with colorectal cancer liver metastasis,to analyze the relationship between gut microbiota and fecal metabolites,and to evaluate the predictive value of relevant markers for the efficacy of neoadjuvant chemotherapy in patients with colorectal cancer liver metastasis.Methods This is a case-control study,34 patients with colorectal cancer liver metastasis who were treated in Qilu Hospital of Shandong University from October 2021 to July 2022 were selected as the research objects,and were divided into chemotherapy effective group(20 cases)and chemotherapy ineffective group(14 cases)according to the efficacy evaluation criteria.Logistic regression was used to construct a prediction model to screen the microbiota and metabolic markers capable of predicting the effect of chemotherapy,and the receiver operating characteristic(ROC)curve and survival analysis curve were plotted to evaluate the predictive effect of related microbiota and metabolites on the efficacy of neoadjuvant chemotherapy.Results There was no significant difference in theαandβdiversity of gut microbiota between the patients in the chemotherapy effective group and in the ineffective group(all P>0.05).In terms of species,the relative abundance of 5 species was up-regulated and 10 species were down-regulated in the chemotherapy-effective group compared with the chemotherapy-ineffective group,and the difference was statistically significant(all P<0.05),among which Prevotella salivae could effectively predict the chemotherapy effect(AUC=0.750,P=0.007),with a sensitivity of 80.0%and a specificity of 71.4%.The overall survival of patients with high abundance(17 cases)was lower than that of patients with low abundance(17 cases)(χ^(2)=5.239,P=0.022).In terms of metabolites,20 metabolites were up-regulated and 4 metabolites were down-regulated in the chemotherapy-effective group compared with the chemoth

关 键 词：结直肠癌 肝转移癌 宏基因组 代谢组学 新辅助化疗 疗效预测 

分 类 号：R735.34[医药卫生—肿瘤]