Prognostic significance of NANOG expression in solid tumors: a meta-analysis

Figures & data

Figure 1 Flowchart of the steps of literature retrieval and selection.

Abbreviations: CNKI, China National Knowledge Infrastructure; IHC, immunohistochemical.

Table 1 Main characteristics of 33 studies in the meta-analysis

Study	Year	Country	Language	No. of patients	Type of tumor	Follow-up (months)	Cutoff method and scores	Outcome measures	NOS scores
Park et al^Citation32	2016	Korea	English	142	NSCLC	NA	SP ≥100	OS (S)/DFS (S)	7
Luo et al^Citation33	2013	China	Chinese	62	NSCLC	36–60	NA	OS (S)	7
Xue et al^Citation7	2016	China	Chinese	89	HCC	36	NA	OS (S)	7
Park et al^Citation32	2016	Korea	English	226	NSCLC	NA	SP ≥100	OS (M)/DFS (M)	7
Li et al^Citation34	2013	China	English	309	NSCLC	52 (7–69.5)	PP ≥5%	OS (M)	7
Chang et al^Citation5	2017	Korea	English	112	NSCLC	NA	SP ≥180	OS (M)	7
Nagata et al^Citation6	2017	Japan	English	208	TNBC	80.7 (20–162)	SP ≥3	OS (S)/DFS (S)	7
Jin et al^Citation30	2016	China	English	312	BC	60	PP ≥1%	OS (M)	7
Nagata et al^Citation31	2014	Japan	English	100	BC	80.7 (20–162)	SP ≥3	OS (S)/DFS (S)	7
Li et al^Citation9	2015	China	English	69	GC	35 (6–50)	SP ≥5	OS (S)/DFS (S)	8
Li et al^Citation23	2014	China	Chinese	69	ESCC	65	PP ≥10%	OS (S)	8
Lu et al^Citation24	2013	China	English	43	PC	NA	SP ≥5	OS (S)	6
Yin et al^Citation25	2012	China	English	228	HCC	60 (1–83)	SP ≥1	OS (S)	7
Lin et al^Citation26	2012	China	English	105	GC	NA	SP ≥2	OS (S)	7
Matsuoka et al^Citation27	2012	Japan	English	253	GC	NA	SP ≥5	OS (S)	6
Hwang et al^Citation10	2014	China	English	41	ESCC	13 (0.3–57.4)	NA	OS (S)	6
Lee et al^Citation28	2015	Korea	English	57	OSCC	35.9 (3–127)	SP ≥4	OS (M)	7
Ravindran et al^Citation15	2015	India	English	60	OSCC	31.9 (14–48)	PP ≥16%	OS (M)/DFS (M)	7
Luo et al^Citation14	2013	China	English	122	NPC	60.1 (8–92)	SP ≥6	OS (S)	7
Chiou et al^Citation29	2008	China	English	52	OSCC	NA	NA	OS (S)	6
Wang et al^Citation8	2018	China	English	144	OSCC	62.97 (24–120)	PP ≥50%	OS (M)	6
Meng et al^Citation11	2010	China	English	175	CRC	NA	SP ≥4	OS (S)	6
Gao et al^Citation12	2016	China	English	47	PC	NA	SP ≥2	OS (S)	6
Kenda Šuster et al^Citation13	2017	Slovenia	English	106	OC	75 (65.8–84.1)	SP ≥3	OS (S)/DFS (S)	6
Elsir et al^Citation20	2014	Sweden	English	42	Astrocytoma	NA	PP ≥50%	OS (M)	8
Elsir et al^Citation20	2014	Sweden	English	71	Astrocytoma	NA	PP ≥50%	OS (M)	8
Vaz et al^Citation16	2014	America	English	100	CRC	69.6	PP ≥26%	OS (S)	6
Xu et al^Citation19	2017	China	English	75	MEC	11–124	PP ≥10%	OS (S)	6
Lee et al^Citation22	2012	Korea	English	74	OC	92 (7–183)	SP ≥4	OS (M)/DFS (S)	7
Siu et al^Citation21	2013	China	English	90	OC	63 (4–209)	SP At mean	OS (S)/DFS (S)	7
Wang et al^Citation37	2018	China	Chinese	78	CC	72 (12–144)	SP >3	OS (M)	7
Ouyang et al^Citation39	2016	China	Chinese	116	HCC	16.5 (3–36)	SP ≥2	OS (M)	8
Zhang et al^Citation38	2018	China	Chinese	60	GC	NA	SP >2	OS (S)/DFS (S)	6
Kim et al^Citation36	2017	Korea	English	62	OSCC	35.5	SP ≥4	OS (M)	7
Rodrigues et al^Citation35	2018	Brazil	English	60	TSCC	NA	SP ≥4	OS (S)	6

Abbreviations: BC, breast cancer; NSCLC, non-small cell lung cancer; TNBC, triple-negative breast cancer; ESCC, esophageal squamous cell carcinoma; OSCC, oral squamous cell carcinoma; HCC, hepatocellular carcinoma; NPC, nasopharyngeal carcinoma; GC, gastric cancer; OC, ovarian cancer; PC, pancreatic cancer; MEC, mucoepidermoid carcinoma; CRC, colorectal cancer; CC, cervical cancer; TSCC, tongue squamous cell carcinoma; PP, percentage of positive cells; SP, staining intensity score and percentage of positive cells; OS, overall survival; DFS, disease-free survival; M, multivariate; S, survival curves; NA, not available.

Table 2 Pooled HRs for overall survival according to subgroup analyses

Categories	Studies (N)	No. of patients	Random-effects model		Heterogeneity
			HR (95% CI) for OS	P-value	I^2 (%)	P-value
Overall survival	35	3,959	2.19 (1.87–2.58)	<0.001	37	<0.001
Nationality
Caucasians	26	2,092	1.87 (1.08–3.23)	0.025	68.7	0.012
Asians	8	1,805	2.26 (1.95–2.62)	<0.001	16.8	0.212
Analysis type
Multivariate	13	1,663	2.16 (1.77–2.62)	<0.001	16.6	0.276
Non-multivariate	22	2,296	2.19 (1.73–2.77)	<0.001	47	0.008
Sample size
≥100	16	2,758	2.09 (1.06–2.74)	<0.001	63.8	<0.001
<100	19	1,201	2.25 (1.86–2.72)	<0.001	0	0.866

Figure 2 Forest plot of the HR for the relationship between high NANOG expression and OS.

Note: Weights are from random-effects analysis.
Abbreviation: OS, poor overall survival.

Figure 3 Subgroup analysis of OS and solid tumor type.

Note: Weights are from random-effects analysis.
Abbreviation: OS, poor overall survival.

Figure 4 Forest plot of HR for high NANOG expression and DFS.

Note: Weights are from random-effects analysis.
Abbreviation: DFS, disease-free survival.

Figure 5 Subgroup analysis of solid tumor type and DFS.

Note: Weights are from random-effects analysis.
Abbreviations: NSCLC, non-small cell lung cancer; DFS, disease-free survival.

Table 3 Meta-analytical results of the associations of high NANOG protein expression level with multiple clinicopathological parameters

Categories	Studies (N)	OR (95% CI)	P-value	Heterogeneity
				I^2 (%)	P-value	Model
Age, in years (>50 vs <50)	8	1.0 (0.79–1.26)	1.00	5	0.39	Fixed effects
Sex (male vs female)	17	1.01 (0.82–1.25)	0.934	0	0.776	Fixed effects
Tumor differentiation (moderate/poor vs good)	18	2.63 (1.52–4.55)	0.001	79.9	<0.001	Random effects
T stage (T1–2 vs T3–4)	7	0.44 (0.20–0.93)	0.031	75.3	<0.001	Random effects
TNM stage (III/IV vs I/II)	16	2.22 (1.42–3.45)	<0.001	55.8	0.004	Random effects
Tumor size (>5 cm vs <5 cm)	4	1.28 (0.53–3.11)	0.13	78.6	0.003	Random effects
Lymph node metastasis (yes vs no)	16	2.59 (1.50–4.47)	0.001	77.6	<0.001	Random effects
Lymphatic infiltration (yes vs no)	4	1.22 (0.44–3.33)	0.703	79.1	0.002	Random effects
Vascular infiltration (yes vs no)	6	0.60 (0.38–1.09)	0.103	48.4	0.084	Fixed effects

Figure 6 Sensitivity analysis of OS.

Abbreviation: OS, poor overall survival.

Figure 7 Sensitive analysis of DFS.

Abbreviation: DFS, disease-free survival.

Figure 8 Begg’s funnel plot of OS and publication bias.

Abbreviation: OS, poor overall survival.

Figure 9 Begg’s funnel plot of DFS and publication.

Abbreviation: DFS, disease-free survival.

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