Expression of Bmi-1 is a prognostic marker in bladder cancer

Abstract

BackgroundThe molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer.MethodsWe examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis.ResultsExpression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P < 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (P < 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (P < 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, P < 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, P > 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P < 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (P < 0.05), but not with tumor number (P > 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P < 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer survival time (P < 0.05).ConclusionExpression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

Knockdown of the Bmi-1 oncogene inhibits cell proliferation and induces cell apoptosis and is involved in the decrease of Akt phosphorylation in the human breast carcinoma cell line MCF-7

“…Bmi-1 may be new diagnostic and prognostic marker in multiple different tumors including medulloblastoma (22), tongue squamous cell carcinoma (23), colon carcinoma (24), breast carcinoma (11), bladder carcinoma (25). However, precise molecular regulation mechanism of Bmi-1 in breast carcinoma remains elusive, promting the authors to investigate the possible molecular ONCOLOGY REPORTS 25: 409-418, 2011 Figure 5.…”

Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance

“…11,12 In previous NSCLC studies, Vonlanthen et al 18 reported no association of Bmi1 expression with tumor characteristics (proliferation rate, differentiation, and size) or prognosis, whereas Vrzalikova et al 20 reported that Bmi1 expression was correlated with advanced stage and poor disease-free survival, but not with overall survival. For other types of cancer, some studies demonstrated that overexpression of Bmi1 was correlated with a poor prognosis [42][43][44] ; however, others reported that loss of Bmi1 expression was correlated with an aggressive phenotype, indicating a protective role of the Bmi1 protein. [45][46][47] Abundant expression of Bmi1 in normal bronchial epithelial cells in the current study and in a previous report 19 and low Bmi1 expression in the majority of tumor cells suggest that Bmi1 may have a protective role in NSCLC.…”

Anti-proliferation effect of BMI-1 in U937 cells with siRNA

“…The results indicate that inhibition of U937 cell proliferation by BMI-1 siRNA is mediated by upregulation of p16 which arrested the cell at G1 to S phase in its cell cycle (25,26). p16Ink4a is a downstream target of Bmi-1 (4,14), and in the absence of Bmi-1 the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated (27). Both flow cytometric apoptosis assay and TUNEL assay showed that Bmi-1 specific siRNA treatment resulted in a significant increase in the percentage of cell apoptosis.…”

“…Bmi-1 is also essential for leukemic stem cells and perhaps other type of cancer stem cells. It is overexpressed in both hematological malignancies (8)(9)(10) and solid tumors such as non-small cell lung cancer (11), liver (12), breast (13), bladder cancer (14), prostate carcinomas (15) and Ewing sarcoma (16). Therefore, BMI-1 plays an important role in regulating the proliferation of both normal and leukemia stem cells, which is useful as a novel molecular marker to predict the progression and prognosis, and may become clinically useful as a noninvasive diagnostic marker (17)(18)(19)(20)(21).…”