Shen Xiaonan, Li Jialu, Li Jiaqi, Zhang Yao, Li Xiaobo, Cui Yun, Gao Qinyan, Chen Xiaoyu, Chen Yingxuan, Fang Jing-Yuan
Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Front Oncol. 2021 May 11;11:661048. doi: 10.3389/fonc.2021.661048. eCollection 2021.
Up to now, non-invasive diagnosis of laterally spreading tumor (LST) and prediction of adenoma recurrence after endoscopic resection of LSTs is inevitable. This study aimed to identify a microbial signature with clinical significance of diagnosing LSTs and predicting adenoma recurrence after LSTs colectomy.
We performed 16S rRNA sequencing in 24 mucosal samples, including 5 healthy controls (HC), 8 colorectal adenoma (CRA) patients, and 11 LST patients. The differentiating microbiota in fecal samples was quantified by qPCR in 475 cases with 113 HC, 208 CRA patients, 109 LST patients, and 45 colorectal cancer (CRC) patients. We identified differentially abundant taxa among cases and controls using linear discriminant analysis effect size analysis. ROC curve was used to evaluate diagnostic values of the bacterial candidates. Pairwise comparison of AUCs was performed by using the Delong's test. The Mantel-Haenszel hazard models were performed to determine the effects of microbial compositions on recurrence free survival.
The microbial dysbiosis of LST was characterized by relative high abundance of the genus Lactobacillus-Streptococcus and the species enterotoxigenic Bacteroides fragilis (ETBF)-Peptostreptococcus stomatis (P. stomatis)-Parvimonas micra (P. micra). The abundance of ETBF, P. stomatis, and P. micra were steadily increasing in LST and CRC groups. P. stomatis behaved stronger value on diagnosing LST than the other two bacteria (AUC 0.887, 95% CI 0.842-0.931). The combination of P. stomatis, P. micra, and ETBF (AUC 0.922, 95% CI 0.887-0.958) revealed strongest diagnostic power with 88.7% sensitivity and 81.4% specificity. ETBF, P. stomatis, and P. micra were associated with malignant LST (P = 0.0015, P = 0.0255, P = 0.0169) and the abundance of IL-6. The high abundance of P. stomatis was related to the adenoma recurrence after LST resection (HR = 3.88, P = 0.008).
Fecal microbiome signature (--) can diagnose LSTs with high accuracy. , , and were related to malignant LST and exhibited high predictive value on the adenoma recurrence after resection of LSTs. The fecal microbiome signature of LST may provide a noninvasive alternative to early detect LST and predict the adenoma recurrence risk after resections of LSTs.
迄今为止，对侧向发育型肿瘤（LST）进行无创诊断以及预测LST内镜切除术后腺瘤复发是必不可少的。本研究旨在识别具有诊断LST及预测LST结肠切除术后腺瘤复发临床意义的微生物特征。
我们对24份黏膜样本进行了16S rRNA测序，包括5名健康对照（HC）、8名结直肠腺瘤（CRA）患者和11名LST患者。通过qPCR对475例患者（113名HC、208名CRA患者、109名LST患者和45名结直肠癌（CRC）患者）粪便样本中的差异微生物群进行定量分析。我们使用线性判别分析效应大小分析来识别病例组和对照组之间差异丰富的分类群。采用ROC曲线评估候选细菌的诊断价值。通过德龙检验对AUC进行两两比较。采用Mantel-Haenszel风险模型来确定微生物组成对无复发生存的影响。
LST的微生物失调特征为乳酸杆菌-链球菌属以及产肠毒素脆弱拟杆菌（ETBF）-口腔消化链球菌（P. stomatis）-微小消化链球菌（P. micra）相对丰度较高。ETBF、P. stomatis和P. micra在LST组和CRC组中的丰度稳步增加。P. stomatis在诊断LST方面比其他两种细菌表现出更强的价值（AUC 0.887，95%CI 0.842-0.931）。P. stomatis、P. micra和ETBF联合检测（AUC 0.922，95%CI 0.887-0.958）显示出最强的诊断能力，敏感性为88.7%，特异性为81.4%。ETBF、P. stomatis和P. micra与恶性LST（P = 0.0015，P = 0.0255，P = 0.0169）及白细胞介素-6的丰度相关。P. stomatis丰度高与LST切除术后腺瘤复发相关（HR = 3.88，P = 0.008）。
粪便微生物组特征（--）能够高精度诊断LST。（--）、（--）和（--）与恶性LST相关，且（--）对LST切除术后腺瘤复发具有较高的预测价值。LST的粪便微生物组特征可能为早期检测LST及预测LST切除术后腺瘤复发风险提供一种无创替代方法。
