Clinicopathological and prognostic significance of epithelial cell transforming sequence 2 expression in cancers: a systematic review and meta-analysis

Figures & data

Figure 1. The process of searching for eligible articles.

Table 1. The main characteristics of included studies.

Reference	Study type	Country	Type of cancer	Case number (high/low ECT2 expression )	Test method	Sub-cellular distribution in tumour cell	TNM III-IV stage (%)	Poor differentiation (%)	Gender (M/F)	Age (years)	Outcome measures	Analysis type	NOS
Bai et al. [15]	R	China	NSCLC	55/35	IHC	Both	NR	NR	NR	NR	OS	Multivariate	6
Chen et al. [37]	R	Singapore	HCC	33/34	IHC	NR	NR	NR	59/8	NR	RFS	Multivariate	6
Chen et al. [19]	R	China	OSM	26/23	IHC	Both	NR	NR	31/18	NR	OS	Multivariate	6
Cheng et al. [20]	R	China	GM	10/67	qPCR	NR	NR	NR	NR	NR	OS	Univariate	6
Guo et al. [38]	R	China	PC	NR	qPCR	NR	32	NR	NR	NR	RFS	Multivariate	6
Hirata et al. [32]	R	Japan	NSCLC	112/130	IHC	Both	NR	NR	166/76	63.3	OS	Multivariate	6
Hirata et al. [32]	R	Japan	EC	81/159	IHC	Both	NR	NR	219/21	61.9	OS	Multivariate	6
Iyoda et al. [21]	R	Japan	OSCC	68/26	IHC	Both	75	4.2	67/29	NR	NR	NR	6
Jin et al. [22]	R	China	GC	79/33	IHC	Both	65.2	61.6	80/32	59.2	OS	Multivariate	7
Kosibaty et al. [33]	R	Japan	LADC	83/84	IHC	Both	13.8	NR	88/79	NR	OS	Multivariate	7
Li et al. [41]	R	China	CRC	44/22	IHC	Both	43.9	22.7	37/29	53	OS	Multivariate	7
Liu et al. [23]	R	Germany	PADC	157/17	qPCR	NR	NR	NR	NR	NR	OS	Univariate	6
Luo et al. [11]	R	China	CRC	203/142	IHC	Both	49.6	NR	199/146	NR	OS	Multivariate	7
Murata et al. [34]	R	Japan	LADC	25/41	IHC	Nucleus	27.3	NR	NR	NR	OS	Multivariate	6
Sano et al. [35]	R	USA	GM	26/28	IHC	NR	NR	NR	30/24	47.6 ± 17.8	OS	Univariate	6
Shi et al. [36]	R	China	NSCLC	175/174	qPCR	NR	50	38	159/190	NR	OS/RFS	Multivariate	6
Wang et al. [39]	R	China	GC	35/15	qPCR	NR	54	74	34/16	NR	NR	NR	6
Wang et al. [24]	R	China	BC	95/70	IHC	Nucleus	49.1	NR	NR	NR	OS	Multivariate	6
Xiu et al. [40]	R	China	BC	1034/368	qPCR	NR	NR	NR	NR	NR	OS	Univariate	6
Zhou et al. [25]	R	China	LADC	318/184	qPCR	NR	21	NR	231/271	NR	OS/RFS	Multivariate	7
Zhou et al. [25]	R	China	LUSC	68/426	qPCR	NR	18	NR	366/128	NR	OS/RFS	Multivariate	7

Note. R: retrospective; ECT2: epithelial cell transforming sequence 2; NOS: Newcastle-Ottawa Scale; NR: not reported; IHC: immunohistochemistry; NSCLC: non-small-cell lung cancer; OS: overall survival; RFS: recurrence‐free survival; HCC: hepatocellular carcinoma; OSM: osteosarcoma; GM: gliomas; PC: prostate cancer; ESCC: oesophageal cancer; OSCC: oral squamous cell carcinoma; GC: gastric cancer; LADC: lung adenocarcinoma; CRC: colorectal cancer; BC: breast cancer; LUSC: lung squamous cell carcinoma; qPCR: quantitative real-time polymerase chain reaction; Both: nucleus and cytoplasm.

Figure 2. Forest plot of the combined HR for the relationship between ECT2 expression and OS in cancer patients. CI: confidence interval; HR: hazard ratio; OS: overall survival; ECT2: epithelial cell transforming sequence 2.

Figure 3. Forest plot of the combined HR for the relationship between ECT2 expression and RFS in cancer patients. CI: confidence interval; HR: hazard ratio; RFS: recurrence-free survival; ECT2: epithelial cell transforming sequence 2.

Figure 4. Forest plot of the OR for the relationship of ECT2 expression to gender. OR: odds ratio; ECT2: epithelial cell transforming sequence 2.

Figure 5. Forest plot of the OR for the relationship of ECT2 expression to age. OR: odds ratio; ECT2: epithelial cell transforming sequence 2.

Figure 6. Forest plot of the OR for the relationship of ECT2 expression to TNM stage. OR: odds ratio; ECT2: epithelial cell transforming sequence 2.

Figure 7. Forest plot of the OR for the relationship of ECT2 expression to lymph node metastasis. OR: odds ratio; ECT2: epithelial cell transforming sequence 2.

Figure 8. Forest plot of the OR for the relationship of ECT2 expression to tumour differentiation. OR: odds ratio; ECT2: epithelial cell transforming sequence 2.

Figure 9. Forest plot of the OR for the relationship of ECT2 expression to distant metastasis. OR: odds ratio; ECT2: epithelial cell transforming sequence 2.

Figure 10. Sensitivity analysis test for the combined HR describing the relationship of ECT2 expression to OS (A) and RFS (B). HR: hazard ratio; OS: overall survival; RFS: recurrence-free survival.

Table 2. Subgroup analysis and meta-regression for HR for the prognostic significance of ETC2 expression.

Variables	No. of studies	Meta-regression			Subgroup analysis		Heterogeneity
		Tau^2	t-Value	p Value	Estimated HR (95% CI)	p Value	p Value	I^2 (%)
Country		0.11	0.33	.75
China	11				2.228(1.759–2.821)	<.01	<.01	61.60%
Japan	4				2.462(1.229–4.933)	.01	<.01	77.20%
Germany	1				2.551(1.460–4.457)	<.01	.	.%
USA	1				2.900(1.234–6.817)	.015	.	.%
Cancer type		0.11	0.98	.34
Digestive system cancers	5				1.896(1.375–2.614)	<.01	.06	55.20%
Non-digestive system cancers	12				2.484(1.900–3.247)	<.01	<.01	64.50%
Sample size		0.97	−1.6	.14
n < 270	12				2.720(1.985–3.727)	<.01	<.01	66.30%
n ≥ 270	5				1.813(1.436–2.287)	<.01	.10	48.40%
Test method		0.1	−0.7	.51
IHC	11				2.435(1.842–3.217)	<.01	<.01	57.60%
qPCR	6				2.069(1.475–2.904)	<.01	<.01	72.70%
Analysis type		0.1	1	.33
Multivariate	13				2.123(1.685–2.674)	<.01	<.01	61.30%
Univariate	4				3.017(1.738–5.236)	<.01	.03	67.60%

Note. qPCR: quantitative real-time polymerase chain reaction; IHC: immunohistochemistry; OS: overall survival; HR: hazard ratio.

Figure 11. Begg’s funnel plot (A) and the adjusted funnel plot (B) for the combined HR describing the relationship of ECT2 expression to OS. CI: confidence interval; HR: hazard ratio; OS: overall survival; ECT2: epithelial cell transforming sequence 2.

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