Low expression of DAB2IP predicts an unfavorable prognosis in human bladder carcinoma

Figures & data

Figure 1 Expression of DOC-2/DAB2 interactive protein (DAB2IP) and phosphorylation signal transducer and activator of transcription 3 (pSTAT3) in UCB tissues and bladder urothelium controls by immunohistochemistry.

Notes: (A) High expression of DAB2IP in normal bladder urothelium. (B) High expression of DAB2IP in low-grade UCB tissue. (C) Low expression of DAB2IP in high-grade UCB tissue. (D) Low expression of p-STAT3 in normal bladder urothelium. (E) High expression of p-STAT3 in low-grade UCB tissue. (F) High expression of p-STAT3 in high-grade UCB tissue. Magnification, 200×.
Abbreviation: UCB, urothelial carcinoma of the bladder.

Figure 2 Relative mRNA levels of DAB2IP and STAT3 in UCB and adjacent non-cancerous tissues.

Notes: (A) Real-time PCR showed that expression of DAB2IP was downregulated in cases of UCB compared with adjacent non-cancerous tissues (P<0.05). Results (mean ± SD) were obtained from three independent experiments. (B) Real-time PCR showed that expression of STAT3 was upregulated in cases of UCB compared with adjacent non-cancerous tissues (P<0.001). Results (mean ± SD) were obtained from three independent experiments. *P<0.05; ***P<0.001.
Abbreviations: PCR, polymerase chain reaction; UCB, urothelial carcinoma of the bladder.

Figure 3 DAB2IP and p-STAT3 expressions in UCB and adjacent non-cancerous tissues.

Notes: Western blot results showed that expression of DAB2IP was downregulated in cases of UCB compared with adjacent non-cancerous tissues. Actin was presented as an internal loading control. Western blot results showed that expression of p-STAT3 was upregulated in cases of UCB compared with adjacent non-cancerous tissues. Actin was presented as an internal loading control. Results of 4 pairs in the total 20 pairs of samples are presented in this figure.
Abbreviation: UCB, urothelial carcinoma of the bladder.

Table 1 Association of DAB2IP expression with clinicopathological factors in UBC patients

Category	All cases, n (%)	DAB2IP, n (%)		P-value
		Low	High
Age				0.241
<65 years	31 (40.3)	19 (61.3)	12 (38.7)
≥65 years	46 (59.7)	34 (73.9)	12 (26.1)
Sex				0.312
Male	70 (90.9)	47 (67.1)	23 (32.9)
Female	7 (9.1)	6 (85.7)	1 (14.3)
Tumor grade				0.016
Low	24 (31.2)	12 (50.0)	12 (50.0)
High	53 (68.8)	41 (77.4)	12 (22.6)
Tumor stage				0.004
Ta+T1	27 (35.1)	13 (48.1)	14 (51.9)
T2+T3+T4	50 (64.9)	40 (80.0)	10 (20.0)
Tumor size				0.821
≥2 cm	59 (76.6)	41 (69.5)	18 (30.5)
<2 cm	18 (23.4)	12 (66.7)	6 (33.3)
Tumor number				0.093
Single	68 (88.3)	49 (72.1)	19 (27.9)
Multiple	9 (11.7)	4 (44.4)	5 (55.6)
Nerve invasion				0.070
Yes	20 (26.0)	17 (85.0)	3 (15.0)
No	57 (74.0)	36 (63.2)	21 (36.8)
Lymphovascular invasion				0.188
Yes	24 (68.8)	19 (79.2)	5 (20.8)
No	53 (31.2)	34 (64.2)	19 (35.8)
Nodal metastasis				0.050
Yes	17 (22.1)	15 (88.2)	2 (11.8)
No	60 (77.9)	38 (63.3)	22 (36.7)
TNM stage				0.037
0+1+2	41 (53.2)	24 (58.5)	17 (41.5)
3+4	36 (46.8)	29 (80.6)	7 (19.4)
Total	77 (100)	53 (68.8)	24 (31.2)

Note: Bold values are statistically significant (P<0.05).

Abbreviation: UBC, urothelial carcinoma of the bladder.

Table 2 Association of p-STAT3 expression with clinicopathological factors in UBC patients

Category	All cases, n (%)	p-STAT3, n (%)		P-value
		Low	High
Age				0.016
<65 years	31 (40.3)	14 (45.2)	17 (54.8)
≥65 years	46 (59.7)	9 (19.6)	37 (80.4)
Sex				0.345
Male	70 (90.9)	22 (31.4)	48 (68.6)
Female	7 (9.1)	1 (14.3)	6 (85.7)
Tumor grade				0.009
Low	24 (31.2)	12 (50.0)	12 (50.0)
High	53 (68.8)	11 (20.8)	42 (79.2)
Tumor stage				0.010
Ta+T1	27 (35.1)	13 (48.1)	14 (51.9)
T2+T3+T4	50 (64.9)	10 (20.0)	40 (80.0)
Tumor size				0.162
≥2 cm	59 (76.6)	20 (33.9)	39 (66.1)
>2 cm	18 (23.4)	3 (16.7)	15 (83.3)
Tumor number				0.010
Single	68 (88.3)	17 (25.0)	51 (75.0)
Multiple	9 (11.7)	6 (66.7)	3 (33.3)
Nerve invasion				0.580
Yes	20 (26.0)	18 (31.6)	39 (68.4)
No	57 (74.0)	5 (25.0)	15 (75.0)
Lymphovascular invasion				0.088
Yes	24 (31.2)	4 (16.7)	20 (83.3)
No	53 (68.8)	19 (35.8)	34 (64.2)
Nodal metastasis				0.212
Yes	17 (22.1)	3 (17.6)	14 (82.4)
No	60 (77.9)	20 (33.3)	40 (66.7)
TNM stage				0.707
0+1+2	41 (53.2)	13 (31.7)	28 (68.3)
3+4	36 (46.8)	10 (27.8)	26 (72.2)
DAB2IP				0.009
Positive	24 (31.2)	12 (50.0)	12 (50.0)
Negative	53 (68.8)	11 (20.8)	42 (79.2)
Total	77 (100)	23 (29.9)	54 (70.1)

Note: Bold values are statistically significant (P<0.05).

Abbreviation: UBC, urothelial carcinoma of the bladder.

Figure 4 Kaplan–Meier curves of OS in bladder cancer based upon T stage, nodal metastasis, and TNM stage.

Notes: (A) Patients with non-muscle-invasive bladder cancer (Ta+T1) had significantly longer OS than those with muscle-invasive bladder cancer (median OS: not reached vs 21.0 months, P=0.002). (B) There was statistically significant difference in OS between the patients with negative and positive nodal metastases (median OS: not reached vs 18.0 months, P<0.001). (C) Patients with early disease stage had significantly longer OS than those with advanced stage (median OS: not reached vs 19.0 months, P<0.001).
Abbreviations: Cum, cumulative; OS, overall survival.

Figure 5 Kaplan–Meier curves of OS in bladder cancer based upon DAB2IP and p-STAT3 expression.

Notes: (A) Patients with DAB2IP expression had significantly longer OS than those without DAB2IP expression (median OS: not reached vs 21.0 months, P=0.001). (B) There was statistically significant difference in OS between the patients with negative and positive p-STAT3 staining (median OS: not reached vs 28.0 months, P=0.033).
Abbreviations: Cum, cumulative; OS, overall survival.

Table 3 Univariate and multivariate Cox regression analyses estimating the associations of DAB2IP expression with patient survival

Category	Crude HR	95% CI	P-value	Adjusted HR	95% CI	P-value
T stage			0.005			0.827
Ta+T1	1			1
T2+T3+T4	4.53	1.58–13.0		0.83	0.18–3.85
Nodal metastasis			<0.001			0.074
No	1			1
Yes	4.00	1.93–8.26		2.00	0.93–4.30
TNM stage			<0.001			0.001
0+1+2	1			1
3+4	5.15	2.2–11.97		4.06	1.73–9.52
DAB2IP			0.003			0.018
Negative	1			1
Positive	0.17	0.05–0.56		0.23	0.07–0.78

Note: Bold values are statistically significant (P<0.05).

Abbreviations: CI, confidence interval; HR, hazard ratio.