Abstract
Several studies have investigated the association between microbial and colorectal cancer (CRC). However, the replicable markers for early stage adenoma diagnosis across multiple populations remain elusive. Here, a meta-analysis of six studies, comprising a total of 1057 fecal samples, was performed to identify candidate markers. By adjusting the potential confounders, 11 and 26 markers (P<0.05) were identified and separately applied into constructing Random Forest classifier models to discriminate adenoma from control, and adenoma from CRC, achieving robust diagnostic accuracy with AUC = 0.80 and 0.89, respectively. Moreover, these markers demonstrated high diagnostic accuracy in independent validation cohorts. Pooled functional analysis and targeted qRT-PCR based genetic profiles reveal that the altered microbiome triggers different pathways of ADP-heptose and menaquinone biosynthesis (P<0.05) in adenoma vs. control and adenoma vs. CRC sequences respectively. The combined analysis of heterogeneous studies confirm adenoma-specific but universal markers across multi-populations, which improves early diagnosis and prompt treatment of CRC.
Competing Interest Statement
The authors have declared no competing interest.
List of abbreviations
- ADP-heptose
- ADP-L-glycero-beta-D-manno-heptose biosynthesis
- ASVs
- amplicon sequence variants
- AUC
- the area under the ROC curve
- BMI
- body mass index
- CD
- Crohn’s disease
- CRC
- Colorectal Cancer
- ENA
- European Nucleotide Archive
- FIT
- Faecal Immunochemical Test
- FOBT
- fecal occult blood test
- IARC
- International Agency for Research on Cancer
- IBD
- Inflammatory bowel disease
- IBS
- Irritable bowel syndrome
- IFE
- Iterative feature elimination
- LODO
- leave-one-dataset-out
- LPS
- lipopolysaccharide
- MAFFT
- Multiple Alignment using Fast Fourier Transform
- MK-10
- menaquinol-10 biosynthesis
- NAFLD
- Non-alcoholic fatty liver disease
- NF-κB
- Nuclear factor-κB
- NSAID
- Nonsteroidal anti-inflammatory drug
- OTUs
- operational taxonomic units
- PICRUSt2
- Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2
- QIIME2
- Quantitative Insights Into Microbial Ecology 2;
- qRT-PCR
- real-time quantitative PCR;
- RF
- Random Forest
- ROC
- Receiver operating characteristic
- SRA
- Sequence Read Archive
- T2D
- type 2 diabetes
- UC
- ulcerative colitis
- WMS
- whole metagenome shotgun sequencing