Clinicohistopathological implications of phosphoserine 9 glycogen synthase kinase-3β/ β-catenin in urinary bladder cancer patients

Table 1 Clinicohistopathological summary of patients with urothelial carcinoma of bladder

Clinicohistopathological variables	n (%)
Total No. of patients	90 (100)
Age (yr) median, range	60, 38-82
N < 60	41.1)
N ≥ 60	53 (58.9)
Gender
Males	88.9)
Females	10 (11.1)
Hematuria
Present	80)
No information	18 (20)
Smoking/tobacco chewing status
Smokers/tobacco chewers	54.4)
Non-smokers/non-tobacco chewers	30)
No information	14 ( 15.6)
Tumor type
UCB	100)
SCC/others	None
Tumor grade
Low	34.4)
High	59 (65.6)
Tumor stage
NMIBC (pTa-pT1)	53.3)
MIBC (pT2-pT3)	42 (46.7)
Lymph node involvement
N0	91.1)
N1	8 (8.9)
Metastasis
M0	91.1)
M1	8 (8.9)
Type
Primary	56.7)
Recurrent	39 (43.3)
Surgical procedure
TURBT	92.2)
Radical cystectomy	(7.8)
Progression	28.2)
Deaths due to cancer	14 (19.7)

UCB: Urothelial carcinoma of bladder; SCC: Squamous cell carcinoma; TURBT: Transurethral resection of bladder; NMIBC: Non-muscle invasive bladder cancer; MIBC: Muscle invasive bladder cancer.

Table 2 Association of aberrant expression of pS9GSK-3β protein with clinicohistopathological factors

Characteristics	pS9GSK-3β (low membranous, no expression or N/C expression)(n = 46/90)
AGE 60 (38-78)	P = 0.87
< 60	20/46
≥ 60	26/46
Stage	P = 0.01a
Non muscle invasive	25/46
Muscle invasive	21/46
Grade	P = 0.04a
Low grade	14/46
High grade	32/46
Type	P = 0.35
Primary	23/46
Recurrent	23/46
Smoking/tobacco chewing	P = 0.66
Yes	24/46
No	14/46
Unknown	8/46
Hematuria	P = 0.64
Present	39/46
Unknown	7/46
Metastasis	P = 0.58
Present	1/46
Absent	45/46

Non parametric Mann Whitney U test was used to determine the P-values.

^aP values ≤ 0.05 are considered as significant. N/C expression: Nuclear/cytoplasmic expression.

Table 3 Association of aberrantly co-expressed pS9GSK-3β and β-Catenin proteins with clinicohistopathological factors in patients with urothelial carcinoma of bladder

Characteristics	pS9GSK-3β + β-Catenin (low membranous, no expression or N/C expression)(n = 28/90)
Age 60 (38-78)	P = 1.0
< 60	11/28
≥ 60	17/28
Stage	P = 0.01a
Non muscle invasive	9/28
Muscle invasive	19/28
Grade	P = 0.09
Low grade	6/28
High grade	22/28
Type	P = 0.02a
Primary	11/28
Recurrent	17/28
Smoking/tobacco chewing	P = 0.04a
Yes	17/28
No	9/28
Unknown	0/28
Hematuria	P = 1.0
Present	23/28
Unknown	5/28
Metastasis	P = 0.9
Present	1/28
Absent	27/28

Non parametric Mann Whitney U test was used to determine the P-values.

^aP values ≤ 0.05 are considered as significant. N/C expression: Nuclear/cytoplasmic expression.

Table 4 Statistical analysis for correlation between expression of target genes at transcriptome level in tumor tissues and clinicohistopathological parameters

	β-Catenin	Cyclin D1	Snail	Slug
Characteristics	Strong expression (n = 57/90)	Strong expression (n = 39/57)	Strong expression (n = 40/57)	Strong expression (n = 42/57)
Age 60 (38-78) yr	p = 0.0071a	P = 0.851	P = 0.585	P = 0.021a
< 60	23/57	17/23	16/23	16/23
≥ 60	34/57	22/34	24/34	26/34
Stage	P = 0.845	P = 0.198	P = 0.205	P = 0.929
Non muscle invasive	34/57	26/34	25/34	25/34
Muscle invasive	23/57	13/23	15/23	17/23
Grade	P = 0.137	P = 0.373	P = 0.420	P = 0.893
Low grade	21/57	16/21	14/21	13/21
High grade	36/57	23/36	26/36	29/36
Type	P = 0.289	P = 0.806	P = 0.62	P = 0.787
Primary	32/57	21/32	22/32	22/32
Recurrent	25/57	18/25	18/25	20/25
Smoking/tobacco chewing	P = 0.738	P = 0.377	P = 0.784	P = 0.592
Yes	26/57	17/26	18/26	20/26
No	18/57	13/18	13/18	14/18
Unknown	13/57	9/13	5/13	8/13
Hematuria	P = 0.397	P = 0.740	P = 0.362	P = 0.685
Present	46/57	32/46	36/46	36/46
Unknown	11/57	7/3	4/3	6/3
Metastasis	P = 0.84	P = 0.39	P = 0.49	P = 0.12
Present	6/57	4/6	4/6	3/6
Absent	51/57	35/51	36/51	39/51

Non parametric Mann Whitney U test and

¹Fisher’s exact probability test were used to determine the P-values;

^aP values ≤ 0.05 are considered as significant.

Table 5 Clinicohistopathological association of nuclear immunoexpressions of Cyclin D1, Slug and Snail proteins in tumors expressing aberrant levels of either pS9GSK-3β or β-catenin proteins

	Aberrant protein expression of either pS9GSK-3β or β-Catenin: n = 61/90
Characteristics	pS9GSK-3βorβ-Catenin (n = 61/90)	Cyclin D1 Strong nuclear expression (n = 15/61)	Cyclin D1 Weak nuclear expression (n = 46/61)	SnailStrong nuclear expression (n = 18/61)	Snail Weak nuclear expression (n = 43/61)	Slug Strong nuclear expression (n = 12/61)	Slug Weak nuclear expression (n = 49/61)
Age 60 (38-78)	P = 0.18	P = 0.03	P = 0.92	P = 0.36	P = 0.17	P = 0.38	P = 0.6
< 60	30/61	9/30	21/30	7/30	23/30	6/30	24/30
≥ 60	31/61	6/31	25/31	11/31	20/31	6/31	25/31
Stage	P = 0.45	P = 0.05a	P = 0.28	P = 0.96	P = 0.37	P = 0.19	P = 0.47
Non muscle invasive	35/61	12/35	23/35	10/35	25/35	7/35	28/35
Muscle invasive	26/61	3/26	23/26	8/26	18/26	5/26	21/26
Grade	P = 0.13	P = 0.01a	P = 0.55	P = 0.96	P = 0.66	P = 0.45	P = 0.90
Low grade	23/61	9/23	14/23	7/23	16/23	6/23	17/23
High grade	38/61	6/38	32/38	11/38	27/38	6/38	32/38
Type	P = 0.1	P = 0.65	P = 0.33	P = 0.42	P = 0.98	P = 0.19	P = 0.13
Primary	33/61	9/33	25/33	9/33	24/33	9/33	24/33
Recurrent	28/61	6/28	21/28	9/28	19/28	3/28	25/28
Smoking/tobacco chewing	P = 0.7	P = 0.29	P = 0.56	P = 0.75	P = 0.16	P = 0.14	P = 0.26
Yes	40/61	11/40	32/40	13/40	27/40	6/40	32/40
No	19/61	4/19	12/19	5/19	14/19	4/19	17/19
Unknown	2/61	0/2	2/2	0/2	2/2	2/2	0/2
Hematuria	P = 0.93	P = 0.53	P = 0.65	P = 0.26	P = 0.62	P = 0.37	P = 0.73
Present	46/61	12/46	34/46	15/46	31/46	9/46	37/46
Unknown	15/61	3/7	12/7	3/7	12/7	3/7	12/7
Metastasis	P = 0.25	P = 0.51	P = 0.53	P = 0.24	P = 0.58	P = 0.26	P = 0.12
Present	5/61	2/5	3/5	3/5	2/5	2/5	3/5
Absent	56/61	13/56	43/56	15/56	41/56	10/56	46/56

Non parametric Mann Whitney U test was used to determine the P-values;

^aP values ≤ 0.05 are considered as significant.