肠道菌群联合血清肿瘤相关物质在鉴别诊断近端结肠癌中的应用  

Gut microbiota aids in differentiating proximal colorectal cancer in the combination of tumor markers

作　　者：黄天臣[1] 韩晓东 张勇[1] 李衎 郭志朋 李磊[1] 武亚超 王雁军[1] 白东晓[1] 肖建安[1] 赵江曼 周福有[1] 李维丽 Huang Tianchen;Han Xiaodong;Zhang Yong;Li Kan;Guo Zhipeng;Li Lei;Wu Yachao;Wang Yanjun;Bai Dongxiao;Xiao Jianan;Zhao Jiangman;Zhou Fuyou;Li Weili(Department of General Surgery,Anyang Oncology Hospital,Anyang 455000,China;Shnaghai Biotecan Biotechnology Co.Ltd.,Shanghai 201204,China)

机构地区：[1]安阳市肿瘤医院普外科,安阳455000 [2]上海宝藤生物医药科技股份有限公司,上海201204

出　　处：《中华检验医学杂志》2024年第4期444-450,共7页Chinese Journal of Laboratory Medicine

基　　金：安阳市科技攻关项目(21161);国家重点研发计划(2018YFE0102400)。

摘　　要：目的探索不同部位结直肠癌肠道菌群的差异以及特征菌联合肿瘤标志物在近端结肠癌中的鉴别效能。方法病例对照研究。选取2019年5月至2022年7月在安阳市肿瘤医院普外科确诊的结直肠癌(CRC)85例和结直肠腺瘤(CRA)患者8例,根据原发部位CRC又分为近端结肠癌组(PC)22例、远端结肠癌组(DC)15例和直肠癌组(RC)48例。肠道准备前采集患者血液和粪便样本分别进行肿瘤标志物检测和16S rDNA基因测序。采用SPSS(27.0.1)软件进行单因素方差分析、Mann-WhitneyU检验、Kruskal-WallisH检验或χ^(2)检验比较组间差异,并利用SPSS对肿瘤标志物、特征菌分别进行单独和联合绘制鉴别PC的受试者工作特征(ROC)曲线。结果PC组、DC组、RC组和CRA组进行组间比较,糖类抗原125(CA125)、CA72-4以及血清肿瘤相关物质(TAM)差异有统计学意义(F=3.543,P<0.05;F=3.596,P<0.05;F=5.787,P<0.01)。其中PC组的CA125水平和CA72-4水平高于RC组[PC组比RC组,(36.84±6.30)kU/L比(12.73±4.21)kU/L,P<0.01;PC组比RC组,(45.56±10.86)kU/L比(3.30±7.63)kU/L,P<0.01],PC组的TAM水平高于RC组和CRA组[PC组比RC组,(124.84±5.19)U/ml比(102.44±3.63)U/ml,P<0.001;PC组比CRA组,(124.84±5.19)U/ml比(95.39±8.42)U/ml,P<0.01]。LEfSe分析显示PC组的特征菌包括拟杆菌科、奈瑟菌科、梭菌科和螺旋体科等。TAM联合拟杆菌科鉴别诊断PC的曲线下面积最大,为0.845(95%CI 0.747~0.944),敏感度为0.857,特异度为0.815。结论不同部位CRC以及CRA间的肠道菌群组成具有异质性,肠道菌群联合肿瘤标志物在区分近端结肠癌中具有良好的鉴别效能。Objective To explore the differences in bacterial community structure between proximal colon cancer(PC),distal colon cancer(DC),and rectal cancer(RC),and the values of featured microbiota in differentiating PC with tumor markers.Methods This case-control study enrolled 85 newly diagnosed colorectal cancer patients,including 22 PC,15 DC and 48 RC patients,and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery,Anyang Oncology Hospital.The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests,respectively.SPSS(27.0.1)was applied to perform the t-test,one-way ANOVA,Mann-Whitney U test,Kruskal-Wallis H test,and Chi-Squared Test.Also,the receiver operating characteristic curve(ROC)was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software.Results All groups had significant differences in the CA125(F=3.543,P<0.05),CA72-4(F=3.596,P<0.05),and serum tumor-associated materials(TAM)levels(F=5.787,P<0.01).In PC group,the levels of CA125[PC vs RC,(36.84±6.30)kU/L vs(12.73±4.21)kU/L,P<0.01]and CA72-4[PC vs RC,(45.56±10.86)kU/L vs(3.30±7.63)kU/L,P<0.01]were significantly higher than that of the RC group,while the level of TAM was remarkably elevated in PC group than in RC group[PC vs RC,(124.84±5.19)U/ml vs(102.44±3.63)U/ml,P<0.001]and CRA group[PC vs CRA,(124.84±5.19)U/ml vs(95.39±8.42)U/ml,P<0.01].The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae,f_Neisseriaceae,f_Clostridiaceae_1,f_Spirochaetaceae,and so on.The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae,which reached 0.845(95%CI 0.747-0.944),with sensitivity being 0.857 and specificity being 0.815.Conclusions There is heterogeneity in gut microbiota composition among PC,DC,RC,and CRA.The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

关 键 词：结直肠肿瘤 肠道菌群 敏感性与特异性 肿瘤标记 生物学 

分 类 号：R735.35[医药卫生—肿瘤]