Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies

Table 1 Potential mechanisms of Fusobacterium nucleatum in gastrointestinal malignancies

Mechanisms	Type of cancer	Potential pathway	Ref.
Release of virulence factors	CRC	Myloid-like FadA	[19]
		FadA/VE-cadherin	[20]
		FadA/E-adherin/β-catenin signaling	[21]
		Fap2/Gal-GalNAC	[22]
		Fn-DPS/ATP3/PD-L1	[23]
		Succinic acid/cGAS-interferon-β pathway	[24]
	EC	Fn-DPS/CCL2/CCL7/EMT	[11]
		Putrescine	[70]
Induction of DNA damage	CRC	E-cadherin and chk2	[26]
		γ-H2AX	[27]
		NEIL2	[28]
	EC	NOD1/RIPK2/NF-κB	[76]
		Senescence-associated secretory phenotype	[25]
Dysregulation of non-coding RNAs	CRC	TLR4/MYD88/NFκB/miRNA21/MAPK	[30]
		miR34a/miR22/miR28	[29]
		miR-31/eukaryotic initiation factor 4f-binding protein 1/2	[32]
		miR-4717/METTL3	[77]
		miR-4474/miR-4717/CREBBP	[78]
		miR-122-5p/FUT8/TGF-1/Smads axis	[36]
		lncRNA EVADR/YBX1	[34]
		lncRNA ENO1-IT1	[33]
	GC	HOTTIP/miR-885-3p	[35]
Modulation of tumor immune microenvironment	CRC	CD11b+ myeloid cells/arginase-1 and iNOS/CD4+T cell	[79]
		miR-1322/polarization of M2 macrophages	[31]
		CEACAM1/T cell and NK cell depletion	[38]
		Fap2/TIGIT/T cell and NK cell depletion	[39]
	EC	NLRP3/MDSCs	[40]
		KIR2DL1/CD8+ T cells	[80]
	PC	CXCL1/CXCR2/MDSCs/CD8+ T cells	[73]
		GM-CSF, CXCL1, IL-8 and MIP-3α	[81]
		AI-2/TNFSF9/CD8+ T cells	[82]
Cooperation with other intestinal microbiota	CRC	Bacteroides fragilis/PKS+E. coli	[42]
		Enterobacteriaceae/Stenotrophomonas	[43]
		Gemella morbillorum/fiber intake	[44]
		RadD/Clostridioides difficile	[83]

EC: Esophageal cancer; CRC: Colorectal cancer; PC: Pancreatic cancer; lncRNAs: Long noncoding RNAs; miRNAs: MicroRNAs; TLR: Toll-like receptor; ENO1-IT1: Enolase1-intronic transcript 1; YBX1: Y-box binding protein 1; MDSCs: Myeloid suppressor cells; NLRP3: NOD-like receptor protein 3; NK cell: Natural killer cell.

Table 2 The detection efficiency of Fusobacterium nucleatum in different gastrointestinal malignancies samples

Cancer	Samples	Risk assessment and detection rate of F. nucleatum	Method	Ref.
CRC	Tissue	72% (proximal) and 35% (distal)	qPCR	[84]
CRC	Tissue	38.8% (54/139)	ddPCR	[85]
CRC	Tissue	56.30% (18/32)	qPCR	[86]
CRC	Tissue	57.1% (8/14)	AP-PCR	[62]
	Saliva	100% (14/14)
CRC	Stool	Worse overall survival	16S rRNA sequencing	[10]
	Tissue
CRC	Tissue	50%	PCR	[87]
	Stool	53.5%
GC	Tissue	26% (19/80)	qPCR	[88]
GC	Tissue	44% (40/91)	qPCR	[89]
GC	Tissue	28.75% (23/80)	qPCR	[66]
		Worse overall survival
EC	Tissue	69.4% (68/98)	qPCR	[71]
PC	Tissue	15.5% (13/84)	qRT-PCR	[73]
PC	Serum	52.4%	ELISA and qPCR	[75]

qPCR: Quantitative polymerase chain reaction; ddPCR: Droplet digtial polymerase chain reaction; AP-PCR: Arbitarily primed polymerase chain reaction; qRT-PCR: Quantitative reverse-transcription polymerase chain reaction; ELISA: Enzyme-linked immunosorbent assay; EC: Esophageal cancer; CRC: Colorectal cancer; PC: Pancreatic cancer.