Prognostic significance of epidermal growth factor receptor expression in glioma patients

Figures & data

Table 1 The main characteristics of the included 17 studies in the meta-analysis

Authors	Publication year	Region	Study design	Tumor type	Range	Detected sample	Assay	Number of patients (male)	Median/mean* (range) or Mean ± SD	Cutoff point (%)	Maximum follow-up time (m)	Survival analysis	Hazard ratios	Quality score	Author’s attitude
Srividya et al^Citation15	2010	India	Prospective	GBM	NA	Tumor tissue/FFPE	IHC	140	47 (18–65)	NA	34	OS	Report	8	Negative
Viana-Pereira et al^Citation16	2008	Portugal	Retrospective	GBM	NA	Tumor tissue/FFPE	IHC	27	NA	10	93	OS	Report	7	Negative
Umesh et al^Citation17	2009	India	Retrospective	GBM	2002	Tumor tissue/FFPE	IHC	54 (41)	46.15* (16–80)	20	53	OS	K–M curve	7	Positive
Choi et al^Citation18	2013	Korea	Retrospective	GBM	1997–2006	Tumor tissue/FFPE	IHC	30 (18)	55.5 (24–77)	10	NA	OS	K–M curve	7	Positive
Nabika et al^Citation19	2010	Japan	Retrospective	AA and GBM	1995–2005	Tumor tissue/FFPE	IHC	59 (35)	61.2±13.3	30	NA	OS	Report	7	Positive
Korshunov et al^Citation20	1999	Russia	Retrospective	GBM	1997–1998	Tumor tissue/FFPE	IHC	168 (95)	50 (18–73)	NA	60	OS	K–M curve	7	Positive
Senetta et al^Citation21	2011	Italy	Retrospective	Ependymoma	2001–2006	Tumor tissue/FFPE	IHC	22 (6)	38.7* (18–63)	20	109	OS	K–M curve	7	Positive
Tini et al^Citation22	2015	Italy	Retrospective	GBM	2008–2013	Tumor tissue/FFPE	IHC	144	63 (35–84)	50	100	OS	K–M curve	7	Positive
Varela et al^Citation23	2004	Argentina	Retrospective	LGG	1995–2000	Tumor tissue/FFPE	IHC	25 (16)	37 (18–72)	10	140	OS	K–M curve	6	Positive
Simmons et al^Citation24	2001	USA	Retrospective	GBM	1987–1995	Tumor tissue/FFPE	IHC	110 (68)	55	NA	75	OS	Report	6	Negative
Saha et al^Citation25	2014	India	Prospective	Astrocytoma	2009–2012	Tumor tissue/FFPE	IHC	57 (45)	NA	15.40	25	OS	K–M curve	7	Positive
Abdullah et al^Citation26	2015	USA	Retrospective	GBM	2003–2013	Tumor tissue	IHC	47	NA	NA	72	OS	K–M curve	6	Positive
Andersson et al^Citation27	2004	Sweden	Retrospective	LGG	NA	Tumor tissue/FFPE	IHC	18	NA	20	180	OS	K–M curve	6	Positive
Etienne et al^Citation28	1998	France	Retrospective	Glioma	1985–1995	Tumor tissue/FFPE	IHC	40	NA	4.60	120	OS	K–M curve	6	Positive
Michaelsen et al^Citation29	2013	Denmark	Retrospective	GBM	2005–2010	Tumor tissue/FFPE	IHC	199	NA	10	60	OS	Report	7	Negative
Mendrzyk et al^Citation30	2006	Russia	Retrospective	Ependymoma	1987–2003	Tumor tissue	IHC	163	NA	NA	120	OS	Report	7	Positive
Chakravarti et al^Citation31	2005	USA	Retrospective	GBM	NA	Tumor tissue/FFPE	IHC	155	NA	MOD 26.3	60	OS	Report	7	Negative

Abbreviations: AA, anaplastic astrocytoma; FFPE, formalin fixed and paraffin embedded; GBM, glioblastoma multiforme; IHC, immunohistochemistry; K–M curve, Kaplan–Meier curve; LGG, low-grade glioma; m, months; MOD, mean optical density; NA, not available; OS, overall survival.

Figure 1 Flow diagram of the study selection process.

Abbreviation: HR, hazard ratio.

Figure 2 Meta-analysis of pooled HRs of OS in gliomas.

Note: Weights are from random-effects analysis.
Abbreviations: CI, confidence interval; HR, hazard ratio; OS, overall survival.

Table 2 Meta-analysis results of subgroups for the OS of gliomas

Subgroup analysis	Number of studies	HR (95% CI)	P-value	Heterogeneity
				I^2 (%)	Ph
OS	17	1.72 (1.32–2.25)	0.000	79.8	0.000
Tumor types
GBM	10	1.57 (1.15–2.14)	0.004	83.8	0.000
LGG	2	1.67 (0.37–7.62)	0.508	0	0.731
Mixed gliomas	5	1.95 (1.45–2.63)	0.000	0	0.522
Publication year
<2010	9	1.95 (1.37–2.77)	0.000	45.6	0.065
≥2010	8	1.52 (1.10–2.10)	0.011	80.2	0.000
Region
Europe	8	1.86 (1.32–2.61)	0.000	53.3	0.036
America	4	1.32 (0.98–1.79)	0.070	0	0.546
Asia	5	1.83 (1.04–3.23)	0.037	85.7	0.000
Study design
Prospective	2	1.47 (0.53–4.08)	0.460	81.1	0.021
Retrospective	15	1.75 (1.39–2.19)	0.000	46.8	0.024
Sample size
<100	10	1.99 (1.54–2.57)	0.000	0	0.501
≥100	7	1.43 (1.04–1.97)	0.027	85.5	0.000
Cutoff value
<20%	6	1.57 (1.02–2.43)	0.041	28.2	0.223
≥20%	5	2.30 (1.49–3.55)	0.000	43.9	0.129
Others and NA	6	1.46 (1.01–2.10)	0.044	83.3	0.000
Maximum follow-up time
<100 m	9	1.55 (1.13–2.12)	0.006	81.8	0.000
≥100 m	6	2.36 (1.71–3.26)	0.000	0	0.976
NA	2	1.56 (1.08–2.25)	0.016	0	0.944
Source of HR
Report	7	1.28 (0.98–1.66)	0.072	69.5	0.003
Kaplan–Meier curves	10	2.10 (1.71–2.58)	0.000	0	0.658
Quality score
<7	5	1.37 (1.00–1.87)	0.048	0	0.618
≥7	12	1.82 (1.31–2.51)	0.000	84.8	0.000

Abbreviations: CI, confidence interval; GBM, glioblastoma multiforme; HR, hazard ratio; LGG, low-grade glioma; m, months; NA, not available; OS, overall survival.

Table 3 Meta-analysis results of subgroups for the OS of GBMs

Subgroup analysis	Number of studies	HR (95% CI)	P-value	Heterogeneity
				I^2 (%)	Ph
OS	10	1.57 (1.15–2.14)	0.004	83.8	0.000
Publication years
<2010	5	1.88 (1.15–3.09)	0.012	68.0	0.014
≥2010	5	1.36 (0.95–1.97)	0.096	82.2	0.000
Region
Europe	4	1.69 (1.09–2.63)	0.018	73.7	0.010
America	3	1.31 (0.96–1.78)	0.086	0	0.381
Asia	3	1.85 (0.63–5.41)	0.262	88.1	0.000
Study design
Prospective	1	0.95 (0.92–0.99)	0.027	/	/
Retrospective	9	1.70 (1.26–2.30)	0.001	64.5	0.004
Sample size
<100	4	2.50 (1.38–4.50)	0.002	42.7	0.156
≥100	6	1.32 (0.97–1.80)	0.078	84.4	0.000
Cutoff value
<20%	3	1.25 (0.77–2.04)	0.370	22.4	0.276
≥20%	2	3.11 (1.15–2.14)	0.003	64.9	0.092
Others and NA	5	1.31 (0.93–1.86)	0.126	80.4	0.000
Maximum follow-up time
<100 m	8	1.47 (1.07–2.02)	0.017	82.0	0.000
≥100 m	1	2.28 (1.50–3.46)	0.000	/	/
NA	1	1.51 (0.55–4.14)	0.424	/	/
Source of HR
Report	5	0.96 (0.92–1.00)	0.077	0.4	0.404
Kaplan–Meier curves	5	2.13 (1.59–2.85)	0.000	33.0	0.202
Quality score
<7	2	1.36 (0.84–2.18)	0.211	48.1	0.165
≥7	8	1.65 (1.13–2.41)	0.009	86.2	0.000

Abbreviations: CI, confidence interval; GBM, glioblastoma multiforme; HR, hazard ratio; m, months; NA, not available; OS, overall survival.

Figure 3 Meta-analysis of pooled HRs of OS in GBM.

Note: Weights are from random-effects analysis.
Abbreviations: CI, confidence interval; GBM, glioblastoma multiforme; HR, hazard ratio; OS, overall survival.

Figure 4 Sensitivity analysis of the relationship between EGFR expression and overall survival in glioma patients.

Abbreviations: CI, confidence interval; EGFR, epidermal growth factor receptor.

Figure 5 Sensitivity analysis of the relationship between EGFR expression and overall survival in GBM patients.

Abbreviations: CI, confidence interval; EGFR, epidermal growth factor receptor; GBM, glioblastoma multiforme.

Figure 6 The funnel plot for all the included studies for overall survival.

Abbreviations: s.e., standard error; InHR, natural logarithm hazard ratio.

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