A novel faecal <i>Lachnoclostridium</i> marker for the non-invasive diagnosis of colorectal adenoma and cancer.

Abstract

There is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma. This study included 1012 subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR. Metagenomic analysis identified '<i>m3</i>' from a <i>Lachnoclostridium</i> sp., <i>Fusobacterium nucleatum</i> (<i>Fn</i>) and <i>Clostridium hathewayi</i> (<i>Ch</i>) to be significantly enriched in adenoma. Faecal <i>m3</i> and <i>Fn</i> were significantly increased from normal to adenoma to CRC (p<0.0001, linear trend by one-way ANOVA) in group I (n=698), which was further confirmed in group II (n=313; p<0.0001). Faecal <i>m3</i> may perform better than <i>Fn</i> in distinguishing adenoma from controls (areas under the receiver operating characteristic curve (AUROCs) <i>m3</i>=0.675 vs <i>Fn</i>=0.620, p=0.09), while <i>Fn</i> performed better in diagnosing CRC (AUROCs <i>Fn</i>=0.862 vs <i>m3</i>=0.741, p<0.0001). At 78.5% specificity, <i>m3</i> and <i>Fn</i> showed sensitivities of 48.3% and 33.8% for adenoma, and 62.1% and 77.8% for CRC, respectively. In a subgroup tested with faecal immunochemical test (FIT; n=642), <i>m3</i> performed better than FIT in detecting adenoma (sensitivities for non-advanced and advanced adenomas of 44.2% and 50.8% by <i>m3</i> (specificity=79.6%) vs 0% and 16.1% by FIT (specificity=98.5%)). Combining with FIT improved sensitivity of <i>m3</i> for advanced adenoma to 56.8%. The combination of <i>m3</i> with <i>Fn</i>, <i>Ch</i>, <i>Bacteroides clarus</i> and FIT performed best for diagnosing CRC (specificity=81.2% and sensitivity=93.8%). This study identifies a novel bacterial marker <i>m3</i> for the non-invasive diagnosis of colorectal adenoma.