Expression and clinical significance of the nin one binding protein and p38 MAPK in prostate carcinoma

Abstract

Background: Prostate carcinoma is a major cause of morbidity and mortality. The MAPK Signaling Pathway plays an important role in multiple tumors, including prostate carcinoma. MAPK signaling is mediated by ERK1/2, JNK and p38 MAPK, which are important in the control of cell proliferation, differentiation and apoptosis. However, relatively little is known about the regulatory mechanism of p38 MAPK in prostate cancers. NOB1 is among the most novel topic in MAPK studies currently. Recent studies found its vital role in tumor metastasis in glioblastoma proliferation, however, its expression profile and its prognostic value in prostate carcinoma have not been investigated.

Methods: To determine the relationship between NOB1 and p38 MAPK expressions, a population-based study was conducted for immunohistochemical staining analysis of tumor tissues, in matched malignant and nonmalignant prostatectomy samples from 132 PCa patients. Moreover, Western blot analysis and NOB1 interference studies of prostate cancer cell lines. To evaluate the diagnostic and prognostic between NOB1 and p38 MAPK in prostate cancer (PCa) tissue after radical prostatectomy, the hypothesis that prostate cancers with NOB1 expression have distinct clinical, prognostic and molecular attributes was tested.

Results: Among 132 prostate cancers, NOB1 expression was detected in 117 (88.7%) tumors by immunohistochemistry. NOB1 and p38 MAPK expression had significant positive correlation with carcinogenesis, tumor progression and patient survival. Immunohistochemically, NOB1 expression in prostate cancer was independently associated with p38 MAPK activation (P=0.0002). Furthermore, p38 MAPK expression was completely suppressed by NOB1 interference in the prostate cancer cell lines DU-145 and PC-3.

Conclusions: NOB1 expression status was closely correlated with important histopathologic characteristics and the recurrence and metastasis of prostate carcinomas. These data support a potential link between NOB1 and p38 MAPK, and suggest that NOB1 may identify a subset of prostate cancer patients with a poor prognosis. This study proved that NOB1 in PCa tissue can be used, in combination with traditional clinicopathological factors, as promising diagnostic and prognostic tools.

Keywords: NOB1; Prostate carcinoma; histopathologic grade; p38 MAPK; prognostic markers.

Figure 1

Immunohistochemical staining of prostate carcinoma for NOB1. Tumor cells showed diffuse strong positive nuclear staining. (A: ×200; B1: ×200; B2: ×400).

Figure 2

Immunohistochemical staining of prostate carcinoma for p38 MAPK. A: Tumor cells showed diffuse positive nuclear staining and some membranous staining. B: Tumor cells showed diffuse positive cytoplasmic staining. (Left: ×200; Right: ×400).

Figure 3

Immunohistochemical staining of prostate carcinoma for p38 MAPK. A: Tumor cells showed diffuse positive membranous staining. B: Tumor cells showed negative membranous staining. (Left: ×200; Right: ×400).

Figure 4

Western blotting analysis of prostate cancer cell lines for NOB1 and p38 MAPK. Each cell line expressed NOB1 and p38 MAPK intensely. After serum starvation for 24 h, NOB1 level was decreased in each cell line nevertheless, p38 level was increased in each cell line.

Figure 5

Effect of NOB1 interference on p38 MAPK expression in prostate cancer cell lines. Significant suppression of p38 MAPK was identified in PC-3 and DU-145, but was not significant in LNCaP. (5 μg siRNA/48 h).

Figure 6

Cumulative survival curves of prostate carcinoma patients by NOB1 expression. NOB1 expression group showed significantly lower survival compared to NOB1 negative group.