Diagnostická přesnost panelu bakteriálních genových markerů (M3) pro kolorektální pokročilou neoplazii (M3-PRO)
Prospektivní průřezová studie k posouzení diagnostické přesnosti panelu bakteriálních genových markerů (M3) pro kolorektální pokročilou neoplazii
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.
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Kontakty a umístění
Studijní místa
-
-
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Hong Kong, Hongkong
- Prince of Wales Hospital
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Metoda odběru vzorků
Studijní populace
Subjects with average risk of colorectal neoplsia requring screening/surveillance colonoscopy
Popis
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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);
Studijní plán
Jak je studie koncipována?
Detaily designu
- Observační modely: CASE_ONLY
- Časové perspektivy: CROSS_SECTIONAL
Kohorty a intervence
Skupina / kohorta |
Intervence / Léčba |
|---|---|
|
Colorectal neoplasia screening/surveillance cohort
Subjects with average risk of colorectal neoplasias requiring screening/surveillance colonoscopy |
A kind of stool test
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Sensitivity of bacterial gene markers panel (M3)
Časové okno: 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. |
1 month
|
|
Sensitivity of FIT/FOBT
Časové okno: 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. |
1 month
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Sensitivity of M3 for early-stage (stage 1) or invasive (stage 2-4) colorectal cancers
Časové okno: 1 month
|
The proportion of subjects with true positive results of M3 among those with early-stage (stage 1) or invasive (stage 2-4) colorectal cancers detected in the index colonoscopy. |
1 month
|
|
Sensitivity of FIT/FOBT for early-stage (stage 1) or invasive (stage 2-4) colorectal cancers
Časové okno: 1 month
|
The proportion of subjects with true positive results of FIT among those with early-stage (stage 1) or invasive (stage 2-4) colorectal cancers detected in the index colonoscopy. |
1 month
|
|
Sensitivity of FIT/FOBT for advanced adenomas
Časové okno: 1 month
|
The proportion of subjects with true positive results of FIT among those with one or more advanced adenomas detected in the index colonoscopy. |
1 month
|
|
Sensitivity of M3 for advanced adenomas
Časové okno: 1 month
|
The proportion of subjects with true positive results of M3 among those with one or more advanced adenomas detected in the index colonoscopy. |
1 month
|
|
Sensitivity of FIT/FOBT for all adenomas
Časové okno: 1 month
|
The proportion of subjects with true positive results of FIT among those with all advanced adenomas detected in the index colonoscopy. |
1 month
|
|
Sensitivity of M3 for all adenomas
Časové okno: 1 month
|
The proportion of subjects with true positive results of M3 among those with all advanced adenomas detected in the index colonoscopy. |
1 month
|
|
Sensitivity of FIT/FOBT for sessile serrated lesions (SSL)
Časové okno: 1 month
|
The proportion of subjects with true positive results of FIT among those with SSLs detected in the index colonoscopy. |
1 month
|
|
Sensitivity of M3 for sessile serrated lesions (SSL)
Časové okno: 1 month
|
The proportion of subjects with true positive results of M3 among those with SSLs detected in the index colonoscopy. |
1 month
|
|
Specificity
Časové okno: 1 month
|
The proportion of true negative results of M3/FOBT/FIT among those with no adenoma detected in colonoscopy |
1 month
|
|
Positive predictive value (PPV)
Časové okno: 1 month
|
The ratio of subjects truly diagnosed as positive to all those who had positive test results |
1 month
|
|
Negative predictive value (NPV)
Časové okno: 1 month
|
The ratio of subjects truly diagnosed as negative to all those who had negative test results |
1 month
|
|
Overall diagnostic accuracy
Časové okno: 1 month
|
The proportion of correctly classified subjects among all subjects |
1 month
|
|
Microbiota changes in subjects with adenomas or normal findings after polypectomy
Časové okno: 1 month
|
Microbiota change measured by qPCR or metagenomic sequencing |
1 month
|
Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 2022.170
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