Bioinformatic analysis of prognostic value of ZW10 interacting protein in lung cancer

Figures & data

Table 1 The basic features of the 15 GEO DataSets databases

Tumor type	Accession number	Sample size (tumor/control)	P-value
Lung cancer	GSE30219	293/14	<0.0001
Lung cancer	GSE31210	226/20	0.0004
Lung cancer	GSE19188	91/65	<0.0001
Melanoma	GSE3189	45/25	<0.0001
Prostate tumor	GSE6919	65/63	<0.0001
Nasopharyngeal carcinoma	GSE12452	31/10	<0.0001
Gastric cancer	GSE13911	38/31	<0.0001
Pancreatic cancer	GSE15471	39/39	<0.0001
Colon tumor	GSE20916	111/34	0.0394
Esophageal carcinoma	GSE23400	53/53	<0.0001
Ovarian cancer	GSE26712	185/10	<0.0001
Pediatric T-ALL	GSE26713	117/7	0.2380
Renal clear cell carcinoma	GSE36895	29/23	<0.0001
Breast cancer	GSE42568	104/17	<0.0001
Liver tumor	GSE14520	225/220	<0.0001

Abbreviations: ZWINT, ZW10 interacting protein; T-ALL, T-cell acute lymphoblastic leukemia.

Table 2 Comparison of ZWINT expression across 17 analyses

Legend	10 datasets	17 analyses	P-value	Fold change
1	Bhattacharjee et al^Citation27	ADC vs normal	0.001	3.074
2		SCLC vs normal	6.18E–6	6.775
3		SCC vs normal	3.42E–8	14.518
4	Garber et al^Citation28	LCC vs normal	2.14E–6	4.530
5		ADC vs normal	3.03E–6	2.903
6		SCLC vs normal	0.002	5.529
7		SCC vs normal	1.26E–6	3.289
8	Hou et al^Citation29	LCC vs normal	8.10E–9	6.357
9		ADC vs normal	6.03E–18	3.961
10		SCC vs normal	4.07E–30	5.798
11	Landi et al^Citation30	ADC vs normal	1.76E–20	2.982
12	Okayama et al^Citation18	ADC vs normal	1.30E–15	2.953
13	Selamat et al^Citation31	ADC vs normal	6.18E–16	1.762
14	Stearman et al^Citation32	ADC vs normal	2.51E–9	3.758
15	Su et al^Citation33	ADC vs normal	5.57E–10	2.696
16	Talbot et al^Citation34	SCC vs normal	2.18E–8	2.471
17	Wachi et al^Citation35	SCC vs normal	1.64E–4	3.455

Abbreviations: GEO, Gene Expression Omnibus; ADC, adenocarcinoma; SCLC, small-cell lung cancer; SCC, squamous cell carcinoma; LCC, large-cell carcinoma.

Figure 1 The expression levels of ZWINT in multiple tumors. ZWINT expression levels were significantly elevated in cancerous, relative to noncancerous tissues, identified in 13 publicly available GEO DataSets databases. ZWINT expression was measured as log2 (probe intensities).

Notes: *P<0.05; **P<0.001.
Abbreviations: ZWINT, ZW10 interacting protein; GEO, Gene Expression Omnibus; T-ALL, T-cell acute lymphoblastic leukemia.

Figure 2 ZWINT was highly expressed in lung cancer patients. (A and B) Real-time PCR analysis of ZWINT expression in 40 lung cancer specimens and adjacent nontumor tissues. (C) Analysis of ZWINT expression in normal lung and different histological subtypes of lung cancer in GSE30219. (D) Oncomine data showing ZWINT expression in lung cancer. (E and F) Analysis of ZWINT expression in normal lung and stage IA lung cancer tissue in GSE31210 and GSE30219. (G) Analysis of ZWINT expression in EGFR-mutated and EGFR-non-mutated lung cancer tissue. β-Actin was used as the internal control for real-time PCR. Experiments were done in triplicate. *P<0.05; **P<0.01.

Abbreviations: ZWINT, ZW10 interacting protein; SCLC, small-cell lung cancer; ADC, adenocarcinoma; SCC, squamous cell carcinoma; LCC, large-cell carcinoma; LCNE, large-cell neuroendocrine tumor; BAS, basaloid; CARCI, carcinoid tumor.

Figure 3 Immunohistochemistry for lung cancer tissues. (A) Representative images of lung cancer patients by immunohistochemistry (magnification: ×10, ×40). (B) H-SCORE of lung cancer and adjacent nontumor tissues. (C) H-SCORE of ADC and SCC.

Note: *P<0.05; ***P<0.001.
Abbreviations: SCC, squamous cell carcinoma; ADC, adenocarcinoma.

Table 3 Correlation between ZWINT expression and the clinicopathological features in GSE30219 with 293 lung cancer patients

Characteristics	No. of patients	ZWINT expression		Chi-square value	P-value
		High	Low
Age (years)				0.314	0.575
≤55	80	42	38
>55	213	104	109
Gender				2.136	0.144
Male	250	129	121
Female	43	17	26
T stage				25.000	<0.0001
1	166	62	104
2	69	42	27
3	31	24	7
4	27	18	9
N stage				34.803	<0.0001
0	198	76	122
1	53	35	18
2–3	42	35	7
M stage				2.379	0.122
0	282	138	144
1	11	8	3
Early recurrencea				15.155	<0.0001
No	164	64	100
Yes	81	53	28
Later recurrence				1.770	0.183
No	164	64	100
Yes	33	17	16

Note:

a Using 2 years as the cutoff, tumor recurrence was classified as either early recurrence or late recurrence.

Abbreviation: ZWINT, ZW10 interacting protein.

Table 4 Correlation between ZWINT expression and the clinicopathological features in GSE31210 with 142 stage I–II primary lung adenocarcinomas patients

Characteristics	No. of patients	ZWINT expression		Chi-square value	P-value
		High	Low
Age (years)				2.961	0.085
≤55	37	23	14
>55	105	48	57
Gender				0.466	0.495
Male	58	31	27
Female	84	40	44
Pathological stage				12.073	0.002
IA	82	35	47
IB	34	15	19
II	26	21	5
Early recurrencea				6.727	0.009
No	110	47	63
Yes	17	13	4
Later recurrence				4.972	0.026
No	110	47	63
Yes	15	11	4

Note:

a Using 2 years as the cutoff, tumor recurrence was classified as either early recurrence or late recurrence.

Abbreviation: ZWINT, ZW10 interacting protein.

Figure 4 Kaplan–Meier survival curves showing the first progression survival based on the expression of ZWINT.

Notes: Survival curves were plotted for (A) all lung cancer patients (n=982), (B) ADC patients (n=461), (C) SCC patients (n=141) and (D) patients with AJCC T1N0M0 stage (n=50). The desired Affymetrix ID was valid: 204026_at (ZWINT). Data were analyzed using Kaplan–Meier plotter (www.kmplot.com).
Abbreviations: ZWINT, ZW10 interacting protein; ADC, adenocarcinoma; SCC, squamous cell carcinoma; AJCC, American Joint Committee on Cancer; HR, hazard ratio.

Figure 5 Kaplan–Meier survival curves indicating overall survival based on the expression of ZWINT.

Notes: Survival curves were plotted for (A) all lung cancer patients (n=1,926), (B) ADC patients (n=720), (C) SCC patients (n=524) and (D) patients with AJCC T1N0M0 stage (n=244). The desired Affymetrix ID was valid: 204026_at (ZWINT). Data were analyzed using Kaplan–Meier plotter (www.kmplot.com).
Abbreviations: ZWINT, ZW10 interacting protein; ADC, adenocarcinoma; SCC, squamous cell carcinoma; AJCC, American Joint Committee on Cancer; HR, hazard ratio.

Table 5 Univariate analyses of clinicopathological parameters and ZWINT expression for recurrence-free survival and overall survival in GSE31210

Variable	Recurrence-free survival		Overall survival
	HR (95% CI)	P-value	HR (95% CI)	P-value
Age (≤55 vs >55 years)	0.907 (0.420–1.962)	0.805	0.579 (0.217–1.645)	0.319
Gender (female vs male)	1.048 (0.517–2.123)	0.896	1.969 (0.733–5.290)	0.179
Smoking (never vs ever)	1.314 (0.657–2.630)	0.440	2.238 (0.813–6.162)	0.119
Pathological stage (IA vs IB vs II)	2.419 (1.595–3.669)	<0.001	2.862 (1.563–5.243)	0.001
ZWINT expression (low vs high)	3.430 (1.540–7.637)	0.003	7.343 (1.668–32.330)	0.008

Abbreviations: ZWINT, ZW10 interacting protein; HR, hazard ratio; CI, confidence interval.

Table 6 Multivariate analyses of clinicopathological parameters and ZWINT expression for recurrence-free survival and overall survival in GSE31210

Variable	Recurrence-free survival		Overall survival
	HR (95% CI)	P-value	HR (95% CI)	P-value
Pathological stage (IA vs IB vs II)	2.069 (1.354–3.162)	0.001	2.308 (1.263–4.218)	0.007
ZWINT expression (low vs high)	2.524 (1.099–5.793)	0.029	5.233 (1.154–23.719)	0.032

Abbreviations: ZWINT, ZW10 interacting protein; HR, hazard ratio; CI, confidence interval.

Figure 6 The interaction network of ZWINT protein with other proteins.

Note: The interaction network was gained from STRING database.
Abbreviations: ZWINT, ZW10 interacting protein; STRING, Search Tool for the Retrieval of Interacting Genes.

Table S1 Clinical information of 40 lung cancer samples

Sample no	Gender	Age (years)	Subtype	TNM
s1	F	44	Adenocarcinoma	T2	N2	M0
s2	M	66	Adenocarcinoma	T2	N0	M0
s3	M	74	Adenocarcinoma	T2	N0	M0
s4	F	64	Adenocarcinoma	T2	N2	M0
s5	F	63	Adenocarcinoma	T1	N0	M0
s6	M	68	Adenocarcinoma	T3	N2	M0
s7	M	74	Adenocarcinoma	T3	N2	M0
s8	F	47	Adenocarcinoma	T3	N2	M0
s9	M	64	Squamous carcinoma	T2	N0	M0
s10	M	63	Squamous carcinoma	T2	N1	M0
s11	M	74	Squamous carcinoma	T3	N2	M0
s12	M	65	Squamous carcinoma	T2	N2	M0
s13	M	55	Squamous carcinoma	T3	N2	M0
s14	M	75	Squamous carcinoma	T2	N2	M0
s15	M	56	Squamous carcinoma	T3	N2	M0
s16	F	57	Adenocarcinoma	T3	N2	M0
s17	F	48	Adenocarcinoma	T2	N2	M0
s18	F	53	Adenocarcinoma	T1	N0	M0
s19	M	58	Squamous carcinoma	T2	N2	M0
s20	M	59	Adenocarcinoma	T2	N2	M0
s21	F	62	Squamous carcinoma	T1	N0	M0
s22	M	51	Squamous carcinoma	T3	N1	M0
s23	F	53	Adenocarcinoma	T3	N2	M0
s24	M	65	Squamous carcinoma	T2	N2	M0
s25	F	45	Adenocarcinoma	T2	N2	M0
s26	F	52	Adenocarcinoma	T1	N0	M0
s27	M	75	Squamous carcinoma	T1	N0	M0
s28	F	54	Adenocarcinoma	T1	N0	M0
s29	M	69	Squamous carcinoma	T2	N0	M0
s30	M	67	Squamous carcinoma	T3	N2	M0
s31	M	68	Squamous carcinoma	T4	N2	M0
s32	M	70	Squamous carcinoma	T3	N2	M0
s33	F	65	Squamous carcinoma	T2	N0	M0
s34	F	75	Adenocarcinoma	T2	N0	M0
s35	M	56	Adenocarcinoma	T2	N0	M0
s36	M	53	Squamous carcinoma	T4	N2	M0
s37	M	63	Squamous carcinoma	T4	N2	M0
s38	F	41	Adenocarcinoma	T1	N0	M0
s39	F	68	Adenocarcinoma	T2	N2	M0
s40	F	74	Adenocarcinoma	T1	N0	M0

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