World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 6, Number 6, December 2015, pages 473-484

GOLPH3 and YB-1 Are Novel Markers Correlating With Poor Prognosis in Prostate Cancer

Figure 1. GOLPH3 protein cytoplasmic expression in different prostatic lesions using IHC. (a) GOLPH3 protein showed positive expression in BPH. (b) Positive GOLPH3 expression in LGPIN. (c) Positive GOLPH3 expression in HGPIN. (d) Positive GOLPH3 expression in PC. Original magnification, × 400 (DAB was used as the chromogen and hematoxylin as counterstain).

Figure 2. YB-1 protein expression in different prostatic lesions using IHC. (a) YB-1 protein showed cytoplasmic expression in BPH. (b) Positive cytoplasmic YB-1 expression in LGPIN. (c) Positive nuclear and cytoplasmic YB-1 expression in HGPIN. (d) Positive cytoplasmic and nuclear YB-1 expression in PC. Original magnification, × 400 (DAB was used as the chromogen and hematoxylin as counterstain).

Figure 3. (a-e) Kaplan-Meier plots for overall survival in PC patients according to Gleason grade (a) and tumor stage (b), GOLPH3 expression (c), nuclear YB-1 (d) and cytoplasmic YB-1 expression (e) with significant P values using log-rank test.

**Table 1.** Patients’ Clinicopathological Parameters in Patients With PC (N = 76)
Clinicopathological parameters	N	%
pT status: pathological tumor stage; pN: lymph node status.
Age (years)
≤ 60	8	10.5
> 60	68	89.5
Baseline PSA (ng/mL)
< 10	13	17.1
10 - 20	39	51.3
> 20	24	31.6
Gleason score
Gleason 2 - 6	17	22.4
Gleason 7	38	50
Gleason 8 - 10	21	27.8
pT status
T2	40	52.6
T3	27	35.5
T4	9	11.8
Perineural invasion
Absent	34	44.7
Present	42	55.3
pN status
No	61	80.3
N1	15	19.7
Stage
I	5	6.6
IIA	18	23.7
IIB	14	18.4
III	21	27.6
IV	18	23.7
Mortality
Alive	30	39.5
Dead	46	60.5

Table 1. Patients’ Clinicopathological Parameters in Patients With PC (N = 76)

Clinicopathological parameters

pT status: pathological tumor stage; pN: lymph node status.

Age (years)

≤ 60

10.5

> 60

89.5

Baseline PSA (ng/mL)

< 10

17.1

10 - 20

51.3

> 20

31.6

Gleason score

Gleason 2 - 6

22.4

Gleason 7

Gleason 8 - 10

27.8

pT status

52.6

35.5

11.8

Perineural invasion

Absent

44.7

Present

55.3

pN status

80.3

19.7

Stage

6.6

IIA

23.7

IIB

18.4

III

27.6

23.7

Mortality

Alive

39.5

Dead

60.5

**Table 2.** Association of GOLPH3 Immunohistochemical Expression With Clinicopathological Parameters in Prostatic Carcinoma (N = 76)
Clinicopathological parameters	Intensity of GOLPH3 expression	P value
Test of significance: Chi-squared and Fischer’s exact tests; P < 0.05 is considered significant. pT status: pathological tumor stage; pN: lymph node status; AR: androgen receptor.
Age (years)			0.508
≤ 60	2 (25)	6 (75)
> 60	22 (32.4)	46 (67.6)
PSA (ng/mL)			0.160
< 10	7 (53.8)	6 (46.2)
10 - 20	11 (28.2)	28 (71.8)
> 20	6 (25)	18 (75)
Gleason score			0.034
Gleason 2 - 6	6 (35.3)	11 (64.7)
Gleason 7	16 (42.1)	22 (57.9)
Gleason 8 - 10	2 (9.5)	19 (90.5)
pT status			0.001
T2	20 (50)	20 (50)
T3	3 (11.1)	24 (88.9)
T4	1 (11.1)	8 (88.9)
Perineural invasion			0.085
Absent	14 (41.2)	20 (58.8)
Present	10 (23.8)	32 (76.2)
pN status			0.017
No	23 (37.7)	38 (62.3)
N1	1 (6.7)	14 (93.3)
Stage			< 0.001
I	4 (80)	1 (20)
IIA	12 (66.7)	6 (33.3)
IIB	5 (35.7)	9 (64.3)
III	2 (9.5)	19 (90.5)
IV	1 (5.6)	17 (94.4)
AR			0.008
Low expression	17 (45.9)	20 (54.1)
High expression	7 (17.5)	32 (82.1)
Mortality			< 0.001
Alive	22 (73.3)	8 (26.7)
Dead	2 (8.3)	44 (84.6)

Table 2. Association of GOLPH3 Immunohistochemical Expression With Clinicopathological Parameters in Prostatic Carcinoma (N = 76)

Clinicopathological parameters

Intensity of GOLPH3 expression

P value

Negative/low (%)

Moderate/intense (%)

Test of significance: Chi-squared and Fischer’s exact tests; P < 0.05 is considered significant. pT status: pathological tumor stage; pN: lymph node status; AR: androgen receptor.

Age (years)

0.508

≤ 60

2 (25)

6 (75)

> 60

22 (32.4)

46 (67.6)

PSA (ng/mL)

0.160

< 10

7 (53.8)

6 (46.2)

10 - 20

11 (28.2)

28 (71.8)

> 20

6 (25)

18 (75)

Gleason score

0.034

Gleason 2 - 6

6 (35.3)

11 (64.7)

Gleason 7

16 (42.1)

22 (57.9)

Gleason 8 - 10

2 (9.5)

19 (90.5)

pT status

0.001

20 (50)

3 (11.1)

24 (88.9)

1 (11.1)

8 (88.9)

Perineural invasion

0.085

Absent

14 (41.2)

20 (58.8)

Present

10 (23.8)

32 (76.2)

pN status

0.017

23 (37.7)

38 (62.3)

1 (6.7)

14 (93.3)

Stage

< 0.001

4 (80)

1 (20)

IIA

12 (66.7)

6 (33.3)

IIB

5 (35.7)

9 (64.3)

III

2 (9.5)

19 (90.5)

1 (5.6)

17 (94.4)

0.008

Low expression

17 (45.9)

20 (54.1)

High expression

7 (17.5)

32 (82.1)

Mortality

< 0.001

Alive

22 (73.3)

8 (26.7)

Dead

2 (8.3)

44 (84.6)

**Table 3.** Association of YB-1 Immunohistochemical Expression With Clinicopathological Parameters in Prostatic Carcinoma (N = 76)
Clinicopathological parameters	Nuclear YB-1 expression	Cytoplasmic YB-1 expression
Test of significance: Chi-squared and Fischer’s exact tests. P < 0.05 is considered significant. pT status: pathological tumor stage; pN: lymph node status; AR: androgen receptor.
Age (years)			0.0129			0.327
≤ 60	7 (87.7)	1 (12.5)		4 (50)	4 (50)
> 60	41 (60.3)	17 (39.7)		24 (35.3)	44 (64.7)
PSA (ng/mL)			0.731			0.237
< 10	9 (69.2)	4 (30.8)		7 (53.8)	8 (46.2)
10 - 20	23 (59)	16 (41)		14 (35.9)	25 (64.1)
> 20	16 (66.7)	8 (33.3)		7 (29.2)	17 (70.8)
Gleason score			0.018			0.008
Gleason 2 - 6	13 (76.5)	4 (23.5)		7 (41.2)	10 (58.8)
Gleason 7	27 (71.1)	11 (28.9)		19 (50)	19 (50)
Gleason 8 - 10	8 (38.1)	13 (61.9)		2 (9.5)	19 (90.5)
pT status			0.428			0.146
T2	28 (70)	12 (30)		18 (45)	22 (55)
T3	15 (55.6)	12 (44.4)		9 (33.3)	18 (66.7)
T4	5 (55.6)	4 (44.4)		1 (11.1)	8 (88.9)
Perineural invasion			0.073			0.173
Absent	25 (73.5)	9 (26.5)		15 (44.1)	19 (55.9)
Present	23 (54.8)	19 (45.2)		13 (31)	25 (69)
pN status			0.277			0.031
No	40 (65.6)	21 (34.4)		26 (42.6)	35 (57.4)
N1	8 (53.3)	7 (46.7)		2 (13.3)	13 (86.7)
Stage			0.136			0.027
I	5 (100)	0 (0)		3 (60)	2 (40)
IIA	13 (72.2)	5 (27.8)		11 (61.1)	7 (38.9)
IIB	10 (71.4)	4 (28.6)		5 (35.7)	9 (64.3)
III	12 (57.1)	9 (42.9)		7 (33.3)	14 (66.7)
IV	8 (44.4)	10 (55.6)		2 (11.1)	16 (88.9)
AR			0.002			< 0.001
Low expression	30 (81.1)	7 (18.9)		22 (59.5)	15 (40.5)
High expression	18 (46.2)	21 (53.8)		6 (15.4)	33 (84.6)
Mortality			0.107			< 0.001
Alive	22 (73.3)	8 (26.7)		20 (66.7)	10 (33.3)
Dead	20 (56.5)	20 (43.5)		8 (17.4)	38 (82.6)

Table 3. Association of YB-1 Immunohistochemical Expression With Clinicopathological Parameters in Prostatic Carcinoma (N = 76)

Clinicopathological parameters

Nuclear YB-1 expression

Cytoplasmic YB-1 expression

Low (%)

High (%)

P value

Low (%)

High (%)

P value

Test of significance: Chi-squared and Fischer’s exact tests. P < 0.05 is considered significant. pT status: pathological tumor stage; pN: lymph node status; AR: androgen receptor.

Age (years)

0.0129

0.327

≤ 60

7 (87.7)

1 (12.5)

4 (50)

> 60

41 (60.3)

17 (39.7)

24 (35.3)

44 (64.7)

PSA (ng/mL)

0.731

0.237

< 10

9 (69.2)

4 (30.8)

7 (53.8)

8 (46.2)

10 - 20

23 (59)

16 (41)

14 (35.9)

25 (64.1)

> 20

16 (66.7)

8 (33.3)

7 (29.2)

17 (70.8)

Gleason score

0.018

0.008

Gleason 2 - 6

13 (76.5)

4 (23.5)

7 (41.2)

10 (58.8)

Gleason 7

27 (71.1)

11 (28.9)

19 (50)

Gleason 8 - 10

8 (38.1)

13 (61.9)

2 (9.5)

19 (90.5)

pT status

0.428

0.146

28 (70)

12 (30)

18 (45)

22 (55)

15 (55.6)

12 (44.4)

9 (33.3)

18 (66.7)

5 (55.6)

4 (44.4)

1 (11.1)

8 (88.9)

Perineural invasion

0.073

0.173

Absent

25 (73.5)

9 (26.5)

15 (44.1)

19 (55.9)

Present

23 (54.8)

19 (45.2)

13 (31)

25 (69)

pN status

0.277

0.031

40 (65.6)

21 (34.4)

26 (42.6)

35 (57.4)

8 (53.3)

7 (46.7)

2 (13.3)

13 (86.7)

Stage

0.136

0.027

5 (100)

0 (0)

3 (60)

2 (40)

IIA

13 (72.2)

5 (27.8)

11 (61.1)

7 (38.9)

IIB

10 (71.4)

4 (28.6)

5 (35.7)

9 (64.3)

III

12 (57.1)

9 (42.9)

7 (33.3)

14 (66.7)

8 (44.4)

10 (55.6)

2 (11.1)

16 (88.9)

0.002

< 0.001

Low expression

30 (81.1)

7 (18.9)

22 (59.5)

15 (40.5)

High expression

18 (46.2)

21 (53.8)

6 (15.4)

33 (84.6)

Mortality

0.107

< 0.001

Alive

22 (73.3)

8 (26.7)

20 (66.7)

10 (33.3)

Dead

20 (56.5)

20 (43.5)

8 (17.4)

38 (82.6)

**Table 4.** Correlations Between Immunohistochemical Markers in Different Lesions
Lesion	Marker expression		GOLPH3	Nuclear YB-1	Cytoplasmic YB-1
Test of significance: Pearson correlation. *Correlation is significant at the 0.01 level (two-tailed). Correlation is significant at the 0.05 level (two-tailed).
BPH	GOLPH3	Pearson correlation	-	0.103	0.649*
Sig. (two-tailed)	-	0.665	0.002
Nuclear YB-1	Pearson correlation	0.103	-	0.116
Sig. (two-tailed)	0.665	-	0.627
Cytoplasmic YB-1	Pearson correlation	0.649*	0.116	-
Sig. (two-tailed)	0.002	0.627	-
PIN	GOLPH3	Pearson correlation	-	0.922**	0.399
Sig. (two-tailed)	-	< 0.001	0.101
Nuclear YB-1	Pearson correlation	0.922**	-	0.559*
Sig. (two-tailed)	< 0.001	-	0.016
Cytoplasmic YB-1	Pearson correlation	0.399	0.559*	-
Sig. (two-tailed)	0.101	0.016	-
Carcinoma	GOLPH3	Pearson correlation	-	0.777**	0.438**
Sig. (two-tailed)	-	< 0.001	< 0.001
Nuclear YB-1	Pearson correlation	0.777**	-	0.611**
Sig. (two-tailed)	< 0.001	-	< 0.001
Cytoplasmic YB-1	Pearson correlation	0.438**	0.611**	-
Sig. (two-tailed)	< 0.001	< 0.001	-

Table 4. Correlations Between Immunohistochemical Markers in Different Lesions

Lesion

Marker expression

GOLPH3

Nuclear YB-1

Cytoplasmic YB-1

Test of significance: Pearson correlation. **Correlation is significant at the 0.01 level (two-tailed). *Correlation is significant at the 0.05 level (two-tailed).

BPH

GOLPH3

Pearson correlation

0.103

0.649*

Sig. (two-tailed)

0.665

0.002

Nuclear YB-1

Pearson correlation

0.103

0.116

Sig. (two-tailed)

0.665

0.627

Cytoplasmic YB-1

Pearson correlation

0.649*

0.116

Sig. (two-tailed)

0.002

0.627

GOLPH3

Pearson correlation

0.922**

0.399

Sig. (two-tailed)

< 0.001

0.101

Nuclear YB-1

Pearson correlation

0.922**

0.559*

Sig. (two-tailed)

< 0.001

0.016

Cytoplasmic YB-1

Pearson correlation

0.399

0.559*

Sig. (two-tailed)

0.101

0.016

Carcinoma

GOLPH3

Pearson correlation

0.777**

0.438**

Sig. (two-tailed)

< 0.001

Nuclear YB-1

Pearson correlation

0.777**

0.611**

Sig. (two-tailed)

< 0.001

Cytoplasmic YB-1

Pearson correlation

0.438**

0.611**

Sig. (two-tailed)

< 0.001

**Table 5.** Multivariate Analyses of Overall Survival in Prostate Carcinoma Patients
Variables	HR	95% CI	P value
Test of significance: Cox regression analysis. P < 0.05 is considered significant. HR: hazard ratio; CI: confidence interval.
Grade	0.840	0.518 - 1.361	0.478
pT status	0.923	0.507 - 1.679	0.792
pN status	0.997	0.359 - 2.515	0.994
Stage	1.574	0.939 - 2.637	0.085
AR	1.086	0.603 - 2.451	0.585
GOLPH3	5.970	1.252 - 28.459	0.025
Nuclear YB-1	1.216	0.603 - 2.451	0.585
Cytoplasmic YB-1	2.100	0.731 - 6.036	0.168

Table 5. Multivariate Analyses of Overall Survival in Prostate Carcinoma Patients

Variables

95% CI

P value

Test of significance: Cox regression analysis. P < 0.05 is considered significant. HR: hazard ratio; CI: confidence interval.

Grade

0.840

0.518 - 1.361

0.478

pT status

0.923

0.507 - 1.679

0.792

pN status

0.997

0.359 - 2.515

0.994

Stage

1.574

0.939 - 2.637

0.085

1.086

0.603 - 2.451

0.585

GOLPH3

5.970

1.252 - 28.459

0.025

Nuclear YB-1

1.216

0.603 - 2.451

0.585

Cytoplasmic YB-1

2.100

0.731 - 6.036

0.168