Table_1_A New Biomarker of Fecal Bacteria for Non-Invasive Diagnosis of Colorectal Cancer.docx

BackgroundThe intestinal flora is correlated with the occurrence of colorectal cancer. We evaluate a new predictive model for the non-invasive diagnosis of colorectal cancer based on intestinal flora to verify the clinical application prospects of the intestinal flora as a new biomarker in non-invasive screening of colorectal cancer. MethodsSubjects from two independent Asian cohorts (cohort I, consisting of 206 colorectal cancer and 112 healthy subjects; cohort II, consisting of 67 colorectal cancer and 54 healthy subjects) were included. A probe-based duplex quantitative PCR (qPCR) determination was established for the quantitative determination of candidate bacterial markers. ResultsWe screened through the gutMEGA database to identify potential non-invasive biomarkers for colorectal cancer, including Prevotella copri (Pc), Gemella morbillorum (Gm), Parvimonas micra (Pm), Cetobacterium somerae (Cs), and Pasteurella stomatis (Ps). A predictive model with good sensitivity and specificity was established as a new diagnostic tool for colorectal cancer. Under the best cutoff value that maximizes the sum of sensitivity and specificity, Gm and Pm had better specificity and sensitivity than other target bacteria. The combined detection model of five kinds of bacteria showed better diagnostic ability than Gm or Pm alone (AUC = 0.861, P < 0.001). These findings were further confirmed in the independent cohort II. Particularly, the combination of bacterial markers and fecal immunochemical test (FIT) improved the diagnostic ability of the five bacteria (sensitivity 67.96%, specificity 89.29%) for patients with colorectal cancer. ConclusionFecal-based colorectal cancer-related bacteria can be used as new non-invasive diagnostic biomarkers of colorectal cancer. Simultaneously, the molecular biomarkers in fecal samples are similar to FIT, have the applicability in combination with other detection methods, which is expected to improve the sensitivity of diagnosis for colorectal cancer, and have a promising prospect of clinical application.背景 肠道菌群与结直肠癌的发生密切相关。本研究针对基于肠道菌群的结直肠癌无创诊断新模型开展评估，旨在验证肠道菌群作为新型生物标志物用于结直肠癌无创筛查的临床应用前景。 方法 本研究纳入两个独立的亚洲队列：队列I包含206例结直肠癌患者与112例健康受试者；队列II包含67例结直肠癌患者与54例健康受试者。本研究建立基于探针的双重定量聚合酶链反应（qPCR）检测方法，用于候选细菌标志物的定量检测。 结果 本研究通过gutMEGA数据库筛选，鉴定出结直肠癌潜在无创生物标志物，包括普通拟杆菌（Prevotella copri, Pc）、莫氏格蓝氏球菌（Gemella morbillorum, Gm）、微小微单胞菌（Parvimonas micra, Pm）、索氏鲸杆菌（Cetobacterium somerae, Cs）以及斯托氏巴斯德菌（Pasteurella stomatis, Ps）。本研究构建了具备良好灵敏度与特异性的预测模型，作为结直肠癌的新型诊断工具。在灵敏度与特异性之和最大化的最佳截断值下，Gm与Pm的特异性与灵敏度均优于其他目标细菌。五种细菌的联合检测模型的诊断性能优于单独使用Gm或Pm（曲线下面积AUC=0.861，P<0.001）。上述研究结果在独立队列II中得到进一步验证。尤为值得注意的是，将细菌标志物与粪便免疫化学测试（FIT）相结合后，五种细菌的诊断性能得到提升（灵敏度67.96%，特异性89.29%），可用于结直肠癌患者的诊断。 结论 粪便来源的结直肠癌相关细菌可作为结直肠癌新型无创诊断生物标志物。同时，粪便样本中的分子标志物与粪便免疫化学测试（FIT）具有相似的应用适用性，可与其他检测方法联合使用，有望提升结直肠癌的诊断灵敏度，具备良好的临床应用前景。