Prognostic value of CD169-positive macrophages in various tumors: a meta-analysis

Figures & data

Figure 1. Flow diagram of the study selection process

Table 1. Baseline characteristics of studies included in the meta-analysis

Study	Origin	Cancer Type	Cases (low/high)	Gender (male/female)	Tumor stage	Median age (range)	Test method	Definition of high or low CD169+ macrophages	Location	Survival results	Maximum months of follow-up
Asano 2018	Japan	Bladder cancer	44 (26/18)	35/9	TNM (I–IV)	70 (49–85)	IHC	Mean number of cells and mean intensity	Regional lymph nodes	OS^MA	133
Hiroto 2018	Japan	Esophageal cancer	182 (101/81)	160/22	TNM (I–IV)	NA	IHC	Mean densities	Regional lymph nodes	OS^MA	140
Li 1# 2017	China	Hepatocellular carcinoma	188 (94/94)	156/29	TNM (I–III)	50 (13–76)	IHC	Mean densities	Intra-tumor	OS^MA	120
Li 2# 2017	China	Gastric cancer	132 (66/66)	95/37	TNM (I–IV)	69 (28–78)	IHC	Mean densities	Intra-tumor	OS^MA	120
Ohnishi 2013	Japan	Colorectal carcinoma	83 (45/38)	48/35	TNM (I–IV)	64 (29–90)	IHC	Mean number of cells	Regional lymph nodes	OS^UA	100
Ohnishi 2016	Japan	Endometrial carcinoma	79 (39/40)	NA	FIGO (I–IV)	59 (30–74)	IHC	Mean number of cells	Regional lymph nodes	OS^UA	120
Saito 2015	Japan	Melanoma	84	36/48	Stage (0–4)	69 (34–91)	IHC	Mean number of cells	Regional lymph nodes	OS^MA	100
Shiota 2016	Japan	Breast Cancer	146	73/73	Stage (1–3)	56 (NA)	IHC	Mean number of cells	Regional lymph nodes	OS^MA, RFS^MA	159
Strömvall 2017	Sweden	Prostate cancer	109 (27/82)	NA	Gleason (6–9)	NA	IHC	Mean densities	Regional lymph nodes	OS^MA	250
Wang 2015	China	Bladder carcinoma	302 (151/151)	262/40	TNM (0-IV)	60 (15–90)	IHC	Mean number of cells and mean intensity	Intra-tumor	OS^MA	82
Zhang 2016	China	Hepatocellular carcinoma	328 (164/164)	292/36	TNM (I–III)	48 (20–78)	IHC	Mean densities	Intra-tumor	OS^MA	96

This means that these two different studies are from the same article.

Abbreviations: NA, not available; IHC, immunohistochemistery; OS, overall survival; RFS, recurrence-free survival; MA, multivariate analysis; UA, univariate analysis.

Table 2. Newcastle -Ottawa Quality Assessment Scale

Author	Year	Selection	Comparability	Outcome	Total
Asano et al.	2018	☆☆	☆☆	☆☆☆	7
Hiroto et al	2018	☆☆	☆☆	☆☆	6
Li et al. 1	2017	☆☆	☆☆	☆☆	6
Li et al. 2	2017	☆☆	☆☆	☆☆	6
Ohnishi et al.	2013	☆	☆☆	☆☆☆	6
Ohnishi et al.	2016	☆☆	☆☆	☆☆☆	7
Saito et al.	2015	☆☆	☆☆	☆☆☆	7
Shiota et al.	2016	☆☆	☆☆	☆☆	6
Stromvall et al.	2017	☆☆	☆☆	☆☆☆	7
Wang et al.	2015	☆	☆☆	☆☆☆	6
Zhang et al.	2016	☆☆	☆☆	☆☆☆	7

Figure 2. Forest plot of the overall survival analysis

Table 3. Subgroup analysis for overall survival

Stratified analysis	No. of cohorts	Pooled HR (95% CI)	P-value	Heterogeneity
				I^2 (%)	P-value	Model
Country
Janpan	6	0.48(0.32, 0.71)	<0.001	0	0.482	Random
China	4	0.66(0.39, 1.12)	0.124	79.9	0.002	Random
Sweden	1	0.21(0.05, 0.90)	0.035	-	-	Random
Tumor type
Digestive system	5	0.52(0.42, 0.67)	<0.001	0	0.877	Random
Urinary system	3	0.42(0.08, 2.34)	0.324	80.5	0.006	Random
Others	3	0.42(0.25, 0.71)	0.001	0	0.370	Random
Sample size
≤ 100	4	0.39(0.24, 0.63)	<0.001	0	0.678	Random
>100	7	0.63(0.41, 0.98)	0.039	67.0	0.006	Random
Definition of high or low
Mean number of cells	4	0.45(0.28, 0.72)	0.001	0	0.515	Random
Mean densities	5	0.50(0.39, 0.65)	<0.001	0	0.629	Random
Both	2	0.56(0.05, 5.95)	0.632	78.6	0.031	Random
Macrophages location
Regional lymph nodes	7	0.45(0.31, 0.66)	<0.001	0	0.471	Random
Intra-tumor	4	0.66(0.39, 1.12)	0.124	79.9	0.002	Random
Analysis type
Univariate	2	0.49(0.21, 1.13)	0.095	0	0.630	Random
Multivariate	9	0.56(0.38, 0.84)	0.004	64.3	0.004	Random
NOS score
≤6	6	0.73(0.45, 1.18)	0.198	64.4	0.015	Random
>6	5	0.42(0.31, 0.58)	<0.001	0	0.597	Random

Table 4. Association between CD169+ macrophages and clinicopathological features

Clinicopathological parameter	No. of cohorts	Model	OR (95% CI)	P-value	Heterogeneity test
					I^2(%)	P-value
Lymph node metastasis (yes vs no)	6	Fixed	0.66(0.47,0.94)	0.020	0.8	0.411
TNM stage (III–IV vs I–II)	7	Fixed	0.62(0.48,0.80)	<0.001	0	0.839
Vascular invasion (yes vs no)	4	Fixed	0.79(0.52,1.20)	0.271	0	0.999
Histological grade (III vs I–II)	4	Fixed	1.26(0.90,1.76)	0.177	41.0	0.165

Figure 3. Sensitivity analysis of overall survival in this meta-analysis

Figure 4. Begg’s funnel plot with pseudo 95% CI of the publication bias for overall survival

Data Availability

The data used to support the findings of this research are available from the corresponding author upon request.