Prognostic role of Toll-like receptors in cancer: a meta-analysis

Figures & data

Figure 1 Flow diagram of the study selection process.

Abbreviations: HR, hazard ratio; TLR, Toll-like receptor.

Table 1 Summary table of the studies included in this meta-analysis

Study year	Origin of population	Disease	Subject number	TLRs	Methods	Cutoff	Survival analysis	HR statistics	Follow-up (months)
Arja Jukkola-Vuorinen et al, 2009^Citation30	Finland	BC	141	TLR9	IHC	Low vs high	OS	R	62.7
Cammarota et al, 2010^Citation11	Italy	CRC	53	TLR4	IHC	Median	DFS	R	0–108
Eiró et al, 2013^Citation12	Spain	CRC	104	TLR4	IHC	Median	RFS	SC	12–316
Eiró et al, 2013^Citation13	Spain	CMM	30	TLR4, 7, 9	IHC	Median	RFS	SC	$36
Eiró et al, 2014^Citation18	Spain	HCC	30	TLR4, 9	IHC	Median	OS	SC	60–204
Wang et al, 2010^Citation24	Japan	CRC	108	TLR4	IHC	Low vs high	DFS	R	–
Ma et al, 2014^Citation22	China	BC	205	TLR4	IHC	Low vs high	DFS	R	98 (2–144)
Grimm et al, 2010^Citation14	Germany	CRC	65	TLR7	IHC	Low vs high	OS	SC	32
Ronkainen et al, 2011^Citation35	Finland	RCC	152	TLR9	IHC	Negative vs positive	OS	R	90 (0–209)
Hirvonen et al, 2016^Citation28	Finland	ACC	32	TLR7	IHC	Median	OS	AP	–
Huhta et al, 2016^Citation19	Finland	EAC	99	TLR4	IHC	Median	OS	SC	36 (0–288)
Zhang et al, 2010^Citation25	China	PDAC	65	TLR4	IHC	Negative vs positive	OS	SC	14 (5–35)
Johanna Korvala et al, 2014^Citation33	Finland	MEC	60	TLR9	IHC	Low vs high	OS	SC	66 (2–303)
Tuomela et al, 2012^Citation36	Finland	BC	231	TLR9	IHC	Low vs high	OS	SC	–
Kauppila, 2014^Citation31	Finland	OTSCC	131	TLR9	IHC	Negative vs positive	OS	R	119 (24–298)
Kauppila et al, 2011^Citation32	USA	EAC	85	TLR9	IHC	Negative vs positive	OS	SC	17.5
Kim et al, 2012^Citation20	Korea	OEC	123	TLR4	IHC	Negative vs positive	OS	SC	43 (3–140)
Leppänen et al, 2017^Citation34	Finland	PC	65	TLR4, 9	IHC	Low vs high	OS	AP	21 (1–60)
Vaisanen, 2012^Citation37	Finland	ProC	242	TLR9	IHC	Negative vs positive	OS	R	–
Własiuk et al, 2013^Citation38	Poland	CLL	41	TLR9	FCM	Low vs high	TFS	SC	57
Petricevic et al, 2012^Citation23	Croatia	BC	133	TLR4	IHC	Negative vs positive	OS	SC	60
Chatterjee et al, 2014^Citation27	France	NSCLC	352	TLR7	IHC	Low vs high	OS	R	–
Ni et al, 2015^Citation29	China	OSCC	166	TLR7	IHC	Low vs high	OS	R	–
Zhe et al, 2016^Citation26	China	HCC	95	TLR4	IHC	Median	OS	R	26.3 (6–36)

Note: –, not available.

Abbreviations: ACC, adenoid cystic carcinoma; AP, author provided; BC, breast cancer; CLL, chronic lymphocytic leukemia; CMM, cutaneous malignant melanoma; CRC, colorectal cancer; DFS, disease-free survival; EAC, esophageal adenocarcinoma; FCM, flow cytometry; HCC, hepatocellular carcinoma; HR, hazard ratio; IHC, immunohistochemistry; MEC, mucoepidermoid carcinoma; NSCLC, non-small-cell lung cancer; OEC, ovarian epithelial cancer; OS, overall survival; OSCC, oral squamous cell carcinoma; OTSCC, oral tongue squamous cell carcinoma; PC, pancreatic cancer; PDAC, pancreatic ductal adenocarcinoma; ProC, prostate cancer; R, reported in the text; RCC, renal cell carcinoma; RFS, relapse-free survival; SC, survival curve; TFS, treatment-free survival; TLR, Toll-like receptor.

Figure 2 Forest plots of studies evaluating hazard ratios of higher expression of TLR4 (A), TLR7 (B), and TLR9 (C) as compared to lower expression in various cancers.

Abbreviation: TLR, Toll-like receptor.

Table 2 Comparison of the predicting value of TLRs’ expression in patients

	TLR4	TLR7	TLR9
Hazard ratio (95% CI)	1.40 (1.09, 1.80)	1.71 (1.38, 2.12)	0.84 (0.62, 1.15)
Heterogeneity, P-value	<0.0001	0.41	<0.00001
Bias, P-value	0.410	0.957	0.757
Model	Random	Fixed	Random
Subject number	1,114	645	1,212
Study number	12	5	11

Abbreviation: TLR, Toll-like receptor.

Figure 3 Funnel plots of studies included in the meta-analyses of TLR4 (A), TLR7 (B), and TLR9 (C).

Abbreviations: SE, standard error; TLR, Toll-like receptor.

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