A Prospective Cross-sectional Multi-center Study to Assess the Diagnostic Accuracy of a Panel of Bacterial Gene Markers (M3) for Colorectal Advanced Neoplasia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,500
- 试验地点
- 1
- 主要终点
- Sensitivity of bacterial gene markers panel (M3)
研究概览
简要总结
The investigators aim to evaluate and compare the diagnostic accuracy of FIT and the novel panel of bacterial gene markers (Fn, m3, Ch and Bc) collectively named as M3, in detecting colorectal advanced neoplasia.
详细描述
Colorectal cancer (CRC) is the one of the most common cancers in Hong Kong with more than 5,500 new cases annually. There is prevailing evidence of increasing trend of young onset CRC globally. Early detection and resection of pre-malignant colorectal neoplasia has shown to reduce CRC-related mortality.
Non-invasive stool tests including guaiac-based faecal occult blood tests (gFOBT) and faecal immunochemical tests (FIT) are the cornerstones of population-based CRC screening programmes. The major limitation of this widely used strategy is its unsatisfactory sensitivities for CRC (79%) and advanced adenomas (AA; 40%). The sensitivity for non-advanced adenomas is even lower than 10%. A large proportion of advanced and non-advanced adenomas will be missed by FIT alone. Therefore, identification of alternative non-invasive test with better sensitivity to detect colorectal neoplasia is warranted.
Multitarget stool DNA test and faecal microbial DNA markers appear to be promising options for CRC screening. Several bacterial gene markers have been identified by metagenome sequencing and reported to be associated with CRC, including Fusobacterium nucleatum (Fn), Clostridium hathewayi (Ch) and Bacteroides clarus (Bc). However, these molecular markers had low accuracy in distinguishing adenomas from normal tissue. Recently, a new Lachnoclostridium gene marker (labelled as 'm3') has been shown to have high diagnostic yield for the detection of colorectal adenomas. In a case-control study of 1012 subjects, a linear increasing trend of m3 level was observed from fecal samples of healthy subjects to those with adenomas and cancers. The overall sensitivity of m3 was significantly higher than FIT in detecting all adenomas (48% vs 9.3%), AA (50.8% vs 16.1%) and non-advanced adenomas (44.2% vs 0%). The diagnostic accuracy of m3 could be further enhanced by combining with a panel of fecal microbial markers composing of Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Clostridium hathewayi (Ch) for CRC (82.3%) and adenomas (64.2%). We hypothesized that the combination of these 4 bacterial gene markers (known as M3) is more sensitive than FIT in detecting colorectal advanced neoplasia.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •They require elective colonoscopy for colorectal cancer screening or polyp surveillance, or investigation of symptoms (e.g. anemia, change of bowel habit, abdominal pain);
- •Aged ≥18 years old;
- •Written informed consent obtained.
排除标准
- •Contraindications to colonoscopy (e.g. perforation, intestinal obstruction, unstable cardiopulmonary status);
- •Contraindication to polyp resection (e.g. active gastrointestinal bleeding, uninterrupted anticoagulation or dual antiplatelets);
- •Known colorectal cancer or adenoma for staged procedure;
- •Previous colonic resection;
- •Personal history of colorectal cancer;
- •Personal history of polyposis syndrome;
- •Personal history of inflammatory bowel disease;
- •Known pregnancy or lactation;
- •Advanced comorbid conditions (defined as American Society of Anesthesiologists grade 4 or above);
结局指标
主要结局
Sensitivity of bacterial gene markers panel (M3)
时间窗: 1 month
The proportion of subjects with true positive results of M3 among those with one of more advanced neoplasia detected in the index colonoscopy.
Sensitivity of FIT/FOBT
时间窗: 1 month
The proportion of subjects with true positive results of FIT among those with one of more advanced neoplasia detected in the index colonoscopy.
次要结局
- Sensitivity of FIT/FOBT for early-stage (stage 1) or invasive (stage 2-4) colorectal cancers(1 month)
- Sensitivity of M3 for all adenomas(1 month)
- Microbiota changes in subjects with adenomas or normal findings after polypectomy(1 month)
- Sensitivity of FIT/FOBT for advanced adenomas(1 month)
- Sensitivity of M3 for advanced adenomas(1 month)
- Sensitivity of FIT/FOBT for all adenomas(1 month)
- Sensitivity of M3 for sessile serrated lesions (SSL)(1 month)
- Overall diagnostic accuracy(1 month)
- Sensitivity of M3 for early-stage (stage 1) or invasive (stage 2-4) colorectal cancers(1 month)
- Positive predictive value (PPV)(1 month)
- Negative predictive value (NPV)(1 month)
- Sensitivity of FIT/FOBT for sessile serrated lesions (SSL)(1 month)
- Specificity(1 month)
研究者
Louis Ho Shing Lau
Assistant Professor (clinical)
Chinese University of Hong Kong