Fusobacterium’s link to colorectal neoplasia sequenced: A systematic review and future insights

Table 2 Studies looking at Fusobacterium associations with colorectal cancer stage and prognosis

Authors	Sample size	CRC depth of invasion	CRC lymph nodes metastasis	CRC metastatic disease	CRC stage	CRC prognosis
Viljoen et al[31]	South African cohort: 55 CRCs.	-	-	-	Association between higher number of F. nucleatum rDNA copies and late stage CRC (stage III and IV compared to stage I and II)	-
Zhou et al[32]	Chinese cohort: 97 CRCs	No association with relative percentage of Fusobacterium rDNA copies	No association with relative percentage of Fusobacterium rDNA copies	No association with relative percentage of Fusobacterium rDNA copies	No association with relative percentage of Fusobacterium rDNA copies	-
Zackular et al[39]	United States and Canadian cohort: 30 CRC, 30 TA, 30 healthy controls	-	-	-	No association with relative percentage of F. nucleatum rDNA copies in CRC	-
Castellarin et al[41]	Canadian cohort: 99 CRCs	-	Association between relative percentage of F. nucleatum rDNA copies in CRC and regional lymph nodes metastasis	-	No association with relative percentage of F. nucleatum rDNA copies in CRC	No association to between relative percentage of F. nucleatum rDNA copies in CRC and CRC overall survival
Chen et al[42]	Chinese cohort: 98 CRCs	-	No association with presence of F. nucleatum rDNA in CRC	-	-	-
Ito et al[46]	Japanese cohort: 544 CRCs	-	-	-	No association with detection or number of F. nucleatum rDNA copies	No association between detection or number of F. nucleatum rDNA copies and CRC overall survival-unknown follow up period
Nosho et al[47]	Japanese cohort: 511 CRCs	-	-	-	No association with detection of F. nucleatum rDNA in CRC	No association between F. nucleatum rDNA presence in CRC and CRC-specific survival-unknown follow up period
Mima et al[48]	United States cohort: 598 CRCs.	-	-	-	-	No relation between F. nucleatum rDNA copies in CRC and CRC-specific survival or CRC overall survival- unknown follow up period
Flanagan et al[50]	Czech, German and Irish cohorts: 122 CRCs	-	-	-	No association with relative percentage of F. nucleatum rDNA copies	Higher relative percentage of F. nucleatum rDNA copies was associated with shorter CRC overall survival within 3-5 years follow up (HR = 19.96, 95%CI: 1.42-281.42) (no adjustment for other confounders)
Li et al[52]	Chinese cohort: 101 CRC	No association	Association between relative percentage of F. nucleatum rDNA copies in CRC and lymph nodes metastasis	-	No association with relative percentage of F. nucleatum rDNA copies in CRC	-
Amitay et al[54]	German cohort: 46 CRC	-	-	-	Relative percentage of F. nucleatum rDNA copies in CRC was associated with advanced stage [stage I vs II (P = 0.012) and stage I vs III (P = 0.042)]	-
Park et al[69]	South Korean cohort: 160 MSI-high CRC.	-	No association with F. nucleatum rDNA detection or number of copies	-	No association with F. nucleatum rDNA detection or number of copies	No association between F. nucleatum rDNA detection or number of copies and disease-free survival
Wei et al[70]	Chinese cohort: 180 CRCs	Association between high relative percentage of F. nucleatum rDNA copies in CRC and depth of invasion	Association between high relative percentage of F. nucleatum rDNA copies in CRC and lymph nodes metastasis	-	-	High relative percentage of F. nucleatum rDNA copies in CRC was associated shorter CRC overall survival within 3 years follow up [HR = 1.993 (1.024 to 3.879)] High relative percentage of F. nucleatum rDNA copies in CRC was associated with shorter CRC disease-free survival within 3 years follow up [HR = 1.829 (1.000 to 3.345)]
Yu et al[71]	Chinese cohort: 88 CRCs	-	F. nucleatum rDNA was more frequently detected in metastatic lymph nodes of proximal vs distal CRC F. nucleatum detected in 100% of metastatic lymph nodes compared to 40% of lymph nodes without metastasis (P < 0.001)	-	-	-
Mima et al[73]	United States cohort: 1069 CRCs	Association between number of F. nucleatum rDNA copies in CRC and higher pT of the TNM staging	No association with number of F. nucleatum rDNA copies in CRC	No association with number of F. nucleatum rDNA copies in CRC	No association with number of F. nucleatum rDNA copies in CRC	High number of F. nucleatum rDNA copies in CRC was associated with shorter CRC-specific survival within 10.7 years follow up [HR = 1.58 (1.04 to 2.39)] for F. nucleatum-high vs F. nucleatum-negative CRCs]. (Multivariable models included CRC stage, age, sex, year of diagnosis, family history of CRC, CRC location, MSI status, CIMP status, KRAS status, BRAF, PIK3CA and CRC LINE-1 methylation.) No association between F. nucleatum rDNA copies in CRC and CRC overall mortality

CRC: Colorectal cancer; CIMP: CpG island methylator phenotype.