Fusobacterium nucleatum Abundance in Tumor Tissue and Stool Samples as a Prognostic Marker in Patients with Colorectal Carcinoma: A Review

Abstract

Fusobacterium nucleatum is an oral anaerobe that turns up, unexpectedly and repeatedly, inside colorectal tumours. Whether measuring it is clinically useful depends on where it is measured, and the tissue and stool literatures have been answering different questions while using the same organism as their subject. Objectives: To review the published evidence on F. nucleatum abundance in colorectal tumour tissue and in stool: what each has been shown to predict, how the two compartments differ in what they can detect, how reproducible the underlying measurements are, and what mechanism has been established. Material and Methods: Narrative review of discovery studies, cohort analyses, diagnostic accuracy studies, meta-analyses and mechanistic work indexed in PubMed and the major oncology, gastroenterology and microbiology journals. Studies were eligible if they reported F. nucleatum abundance or
presence in colorectal tissue or stool with a defined comparator, outcomes stratified by that measure, or mechanism bearing on a clinical observation. No new patient data were generated; every frequency, accuracy estimate and effect size quoted is one published by the original investigators. Results: Over-representation of F. nucleatum in tumour relative to adjacent normal tissue was first reported in 2012 by two groups independently. A systematic review of 45 articles found substantially higher odds of the organism being present in colorectal tumour tissue than in control tissue, with a pooled odds ratio of 10.06, and an association between tumour positivity and worse overall survival, with a pooled hazard ratio of 1.87 across five studies which rose to 2.25 and lost all heterogeneity when the largest study was excluded. In stool, faecal F. nucleatum alone distinguished colorectal cancer from controls with 80.2 per cent sensitivity and 80.7 per cent specificity, rising to 92.8 per cent sensitivity when combined with faecal immunochemical testing and three further bacterial markers. Faecal abundance was 132 times higher in cancer than in controls but only 3.8 times higher in advanced adenoma. Mechanistically, the organism promotes chemoresistance through Toll-like receptor signalling and autophagy activation, and persists in matched liver metastases. Conclusion: Tissue abundance carries a reproducible but moderate prognostic signal whose pooled estimate rests on a small number of studies with substantial heterogeneity. Stool abundance performs respectably for detecting established cancer and poorly for the precursor lesions that screening exists to find. Neither measurement is yet ready to alter management, and the more immediately actionable finding is mechanistic rather than prognostic. Abbreviations: CRC – Colorectal Cancer, Fn – Fusobacterium nucleatum, FIT – Faecal Immunochemical Test, qPCR – Quantitative Polymerase Chain
Reaction, ddPCR – Droplet Digital Polymerase Chain Reaction, MSI – Microsatellite Instability, dMMR – Deficient Mismatch Repair, CIMP – CpG Island Methylator Phenotype, OS – Overall Survival, HR – Hazard Ratio, OR – Odds Ratio, TLR – Toll-Like Receptor.