Skip to main content
Top
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

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

Authors: Zi-Ke Qin, Jian-An Yang, Yun-lin Ye, Xing Zhang, Li-Hua Xu, Fang-Jian Zhou, Hui Han, Zuo-Wei Liu, Li-Bing Song, Mu-Sheng Zeng

Published in: BMC Cancer | Issue 1/2009

Login to get access

Abstract

Background

The 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.

Methods

We 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.

Results

Expression 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).

Conclusion

Expression 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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Greenlee RT, Hi-Harmon MB, Murray T, Thun M: Cancer Statistics, 2001. CA Cancer J Clin. 2001, 51: 15-36. 10.3322/canjclin.51.1.15.CrossRefPubMed Greenlee RT, Hi-Harmon MB, Murray T, Thun M: Cancer Statistics, 2001. CA Cancer J Clin. 2001, 51: 15-36. 10.3322/canjclin.51.1.15.CrossRefPubMed
2.
go back to reference Laufer M, Ramalingam S, Schoenberg MP, Haisfield-Wolf ME, Zuhowski EG, Trueheart IN, Eisenberger MA, Nativ O, Egorin MJ: Intravesical Gemcitabine therapy for superficial transitional cell carcinoma of the bladder phase I and pharmacokinetic study. J Clin Oncol. 2003, 21: 697-703. 10.1200/JCO.2003.09.028.CrossRefPubMed Laufer M, Ramalingam S, Schoenberg MP, Haisfield-Wolf ME, Zuhowski EG, Trueheart IN, Eisenberger MA, Nativ O, Egorin MJ: Intravesical Gemcitabine therapy for superficial transitional cell carcinoma of the bladder phase I and pharmacokinetic study. J Clin Oncol. 2003, 21: 697-703. 10.1200/JCO.2003.09.028.CrossRefPubMed
3.
go back to reference Stein JP, Grossfeld GD, Ginsberg DA, Esrig D, Freeman JA, Figueroa AJ, Skinner DG, Cote RJ: Prognostic markers in bladder cancer: a contemporary review of the literature. J Urol. 1998, 160: 645-659. 10.1016/S0022-5347(01)62747-2.CrossRefPubMed Stein JP, Grossfeld GD, Ginsberg DA, Esrig D, Freeman JA, Figueroa AJ, Skinner DG, Cote RJ: Prognostic markers in bladder cancer: a contemporary review of the literature. J Urol. 1998, 160: 645-659. 10.1016/S0022-5347(01)62747-2.CrossRefPubMed
4.
go back to reference Eissa S, Kassim S, EI-Almady O: Detection of bladder tumours role of cytology, morphology-based assays, biochemical and molecular markers. Cuur Opin Obstet Gynecol. 2003, 15: 395-403. 10.1097/00001703-200310000-00008.CrossRef Eissa S, Kassim S, EI-Almady O: Detection of bladder tumours role of cytology, morphology-based assays, biochemical and molecular markers. Cuur Opin Obstet Gynecol. 2003, 15: 395-403. 10.1097/00001703-200310000-00008.CrossRef
5.
go back to reference Shinka T, Ogura H, Morita T, Nishikawa T, Fujinaga T, Ohkawa T: Relationship between glutathione S-transferase M1 deficiency and urothelial cancer in dye workers exposed to aromatic amine. J Urol. 1998, 159: 380-383. 10.1016/S0022-5347(01)63924-7.CrossRefPubMed Shinka T, Ogura H, Morita T, Nishikawa T, Fujinaga T, Ohkawa T: Relationship between glutathione S-transferase M1 deficiency and urothelial cancer in dye workers exposed to aromatic amine. J Urol. 1998, 159: 380-383. 10.1016/S0022-5347(01)63924-7.CrossRefPubMed
6.
go back to reference Shariat SF, Karam JA, Lerner SP: Molecular markers in bladder cancer. Curr Opin Urol. 2008, 18: 1-8. 10.1097/MOU.0b013e3282f9b3e5.CrossRefPubMed Shariat SF, Karam JA, Lerner SP: Molecular markers in bladder cancer. Curr Opin Urol. 2008, 18: 1-8. 10.1097/MOU.0b013e3282f9b3e5.CrossRefPubMed
7.
go back to reference Haupt Y, Alexander WS, Barri G, Klinken SP, Adans JM: Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in Emu-myc transgenic mice. Cell. 1991, 65: 753-763. 10.1016/0092-8674(91)90383-A.CrossRefPubMed Haupt Y, Alexander WS, Barri G, Klinken SP, Adans JM: Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in Emu-myc transgenic mice. Cell. 1991, 65: 753-763. 10.1016/0092-8674(91)90383-A.CrossRefPubMed
8.
go back to reference van Lohuizen M, Verbeek S, Scheijen B, Wientjens E, van der Gulden H, Bems A: Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991, 65: 737-752. 10.1016/0092-8674(91)90382-9.CrossRefPubMed van Lohuizen M, Verbeek S, Scheijen B, Wientjens E, van der Gulden H, Bems A: Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991, 65: 737-752. 10.1016/0092-8674(91)90382-9.CrossRefPubMed
9.
go back to reference Lugt van der NM, Domen J, Linder sK, van Roon M, Robanus-Maandag E, te Riele H, Valk van der M, Deschamps J, Sofroniew M, van Lohuizen M: Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 1994, 8: 757-769. 10.1101/gad.8.7.757.CrossRefPubMed Lugt van der NM, Domen J, Linder sK, van Roon M, Robanus-Maandag E, te Riele H, Valk van der M, Deschamps J, Sofroniew M, van Lohuizen M: Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 1994, 8: 757-769. 10.1101/gad.8.7.757.CrossRefPubMed
10.
go back to reference Pirrotta V: Polycombing the genome: PcG, trxG, and chromatin silencing. Cell. 1998, 93: 333-336. 10.1016/S0092-8674(00)81162-9.CrossRefPubMed Pirrotta V: Polycombing the genome: PcG, trxG, and chromatin silencing. Cell. 1998, 93: 333-336. 10.1016/S0092-8674(00)81162-9.CrossRefPubMed
11.
go back to reference Lessard J, Sauvageau G: Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003, 423: 255-60. 10.1038/nature01572.CrossRefPubMed Lessard J, Sauvageau G: Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003, 423: 255-60. 10.1038/nature01572.CrossRefPubMed
12.
go back to reference Saito M, Handa K, Kiyono T, Hattori S, Yokoi T, Tsubakimoto T, Harada H, Noguchi T, Toyoda M, Sato S, Teranaka T: Immortalization of cementoblast progenitor cells with Bmi-1 and TERT. J Bone Miner Res. 2005, 20: 50-57. 10.1359/JBMR.041006.CrossRefPubMed Saito M, Handa K, Kiyono T, Hattori S, Yokoi T, Tsubakimoto T, Harada H, Noguchi T, Toyoda M, Sato S, Teranaka T: Immortalization of cementoblast progenitor cells with Bmi-1 and TERT. J Bone Miner Res. 2005, 20: 50-57. 10.1359/JBMR.041006.CrossRefPubMed
13.
go back to reference Mori T, Kiyono T, Imabayashi H, Takeda Y, Tsuchiya K, Miyoshi S, Makino H, Matsumoto K, Saito H, Ogawa S, Sakamoto M, Hata J, Umezawa A: Combination of hTERT and bmi-1, E6, or E7 induces prolongation of the life span of bone marrow stromal cells from an elderly donor without affecting their neurogenic potential. Mol Cell Biol. 2005, 25: 5183-5195. 10.1128/MCB.25.12.5183-5195.2005.CrossRefPubMedPubMedCentral Mori T, Kiyono T, Imabayashi H, Takeda Y, Tsuchiya K, Miyoshi S, Makino H, Matsumoto K, Saito H, Ogawa S, Sakamoto M, Hata J, Umezawa A: Combination of hTERT and bmi-1, E6, or E7 induces prolongation of the life span of bone marrow stromal cells from an elderly donor without affecting their neurogenic potential. Mol Cell Biol. 2005, 25: 5183-5195. 10.1128/MCB.25.12.5183-5195.2005.CrossRefPubMedPubMedCentral
14.
go back to reference Beà S, Tort F, Pinyol M, Puig X, Hernández L, Hernández S, Fernandez PL, van Lohuizen M, Colomer D, Campo E: BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res. 2001, 61: 2409-2412.PubMed Beà S, Tort F, Pinyol M, Puig X, Hernández L, Hernández S, Fernandez PL, van Lohuizen M, Colomer D, Campo E: BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res. 2001, 61: 2409-2412.PubMed
15.
go back to reference Vonlanthen S, Heighway J, Altermatt HJ, Gugger M, Kappeler A, Borner MM, van Lohuizen M, Betticher DC: The bmi-1 oncoprotein is differentially expressed in nonsmall cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer. 2001, 84: 1372-1376. 10.1054/bjoc.2001.1791.CrossRefPubMedPubMedCentral Vonlanthen S, Heighway J, Altermatt HJ, Gugger M, Kappeler A, Borner MM, van Lohuizen M, Betticher DC: The bmi-1 oncoprotein is differentially expressed in nonsmall cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer. 2001, 84: 1372-1376. 10.1054/bjoc.2001.1791.CrossRefPubMedPubMedCentral
16.
go back to reference van Kemenade FJ, Raaphorst FM, Blokzijl T, Fieret E, Hamer KM, Satijn DP, Otte AP, Meijer CJ: Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood. 2001, 97: 3896-3910. 10.1182/blood.V97.12.3896.CrossRefPubMed van Kemenade FJ, Raaphorst FM, Blokzijl T, Fieret E, Hamer KM, Satijn DP, Otte AP, Meijer CJ: Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood. 2001, 97: 3896-3910. 10.1182/blood.V97.12.3896.CrossRefPubMed
17.
go back to reference Kim JH, Yoon SY, Jeong SH, Kim SY, Moon SK, Joo JH, Lee Y, Choe IS, Kim JW: Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. Breast. 2004, 13: 383-388. 10.1016/j.breast.2004.02.010.CrossRefPubMed Kim JH, Yoon SY, Jeong SH, Kim SY, Moon SK, Joo JH, Lee Y, Choe IS, Kim JW: Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. Breast. 2004, 13: 383-388. 10.1016/j.breast.2004.02.010.CrossRefPubMed
18.
go back to reference Cui H, Hu B, Li T, Ma J, Alam G, Gunning WT, Ding HF: Bmi-1 is essential for the tumorigenicity of neuroblastoma cells. Am J Pathol. 2007, 170: 1370-1378. 10.2353/ajpath.2007.060754.CrossRefPubMedPubMedCentral Cui H, Hu B, Li T, Ma J, Alam G, Gunning WT, Ding HF: Bmi-1 is essential for the tumorigenicity of neuroblastoma cells. Am J Pathol. 2007, 170: 1370-1378. 10.2353/ajpath.2007.060754.CrossRefPubMedPubMedCentral
19.
go back to reference Mihara K, Chowdhury M, Nakaju N, Hidani S, Ihara A, Hyodo H, Yasunaga S, Takihara Y, Kimura A: Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and prognosis of the patients. Blood. 2006, 107: 305-308. 10.1182/blood-2005-06-2393.CrossRefPubMed Mihara K, Chowdhury M, Nakaju N, Hidani S, Ihara A, Hyodo H, Yasunaga S, Takihara Y, Kimura A: Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and prognosis of the patients. Blood. 2006, 107: 305-308. 10.1182/blood-2005-06-2393.CrossRefPubMed
20.
go back to reference Song LB, Zeng MS, Liao WT, Zhang L, Mo HY, Liu WL, Shao JY, Wu QL, Li MZ, Xia YF, Fu LW, Huang WL, Dimri GP, Band V, Zeng YX: Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Res. 2006, 66: 6225-6232. 10.1158/0008-5472.CAN-06-0094.CrossRefPubMed Song LB, Zeng MS, Liao WT, Zhang L, Mo HY, Liu WL, Shao JY, Wu QL, Li MZ, Xia YF, Fu LW, Huang WL, Dimri GP, Band V, Zeng YX: Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Res. 2006, 66: 6225-6232. 10.1158/0008-5472.CAN-06-0094.CrossRefPubMed
21.
go back to reference Breuer RH, Snijders PJ, Sutedja GT, Sewalt RG, Otte AP, Postmus PE, Meijer CJ, Raaphorst FM, Smit EF: Expression of the p16(INK4a) gene product, methylation of the p16(INK4a) promoter region and expression of the polycomb-group gene BMI-1 in squamous cell lung carcinoma and premalignant endobronchial lesions. Lung Cancer. 2005, 48: 299-306. 10.1016/j.lungcan.2004.11.026.CrossRefPubMed Breuer RH, Snijders PJ, Sutedja GT, Sewalt RG, Otte AP, Postmus PE, Meijer CJ, Raaphorst FM, Smit EF: Expression of the p16(INK4a) gene product, methylation of the p16(INK4a) promoter region and expression of the polycomb-group gene BMI-1 in squamous cell lung carcinoma and premalignant endobronchial lesions. Lung Cancer. 2005, 48: 299-306. 10.1016/j.lungcan.2004.11.026.CrossRefPubMed
22.
go back to reference Greene FL, Balch CM, Fleming ID, Fritz A, Haller DG, Morrom M, David L: AJCC Cancer Staging Manual. 2002, New York: AJCC Springer-Verlag, 335-340. 6CrossRef Greene FL, Balch CM, Fleming ID, Fritz A, Haller DG, Morrom M, David L: AJCC Cancer Staging Manual. 2002, New York: AJCC Springer-Verlag, 335-340. 6CrossRef
23.
go back to reference Silva J, García V, García JM, Peña C, Domínguez G, Díaz R, Lorenzo Y, Hurtado A, Sánchez A, Bonilla F: Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patients. Breast Cancer Res. 2007, 9: 55-10.1186/bcr1760.CrossRef Silva J, García V, García JM, Peña C, Domínguez G, Díaz R, Lorenzo Y, Hurtado A, Sánchez A, Bonilla F: Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patients. Breast Cancer Res. 2007, 9: 55-10.1186/bcr1760.CrossRef
24.
go back to reference Chowdhury M, Mihara K, Yasunaga S, Ohtaki M, Takihara Y, Kimura A: Expression of Polycomb-group (PcG) protein BMI-1 predicts prognosis in patients with acute myeloid leukemia. Leukemia. 2007, 21: 1116-1122.PubMed Chowdhury M, Mihara K, Yasunaga S, Ohtaki M, Takihara Y, Kimura A: Expression of Polycomb-group (PcG) protein BMI-1 predicts prognosis in patients with acute myeloid leukemia. Leukemia. 2007, 21: 1116-1122.PubMed
25.
go back to reference Sandberg AA, Berger CS: Review of chromosome studies in urological tumors. Cytogenetics andmolecular genetics of bladder cancer. J Urol. 1994, 151: 545-560.PubMed Sandberg AA, Berger CS: Review of chromosome studies in urological tumors. Cytogenetics andmolecular genetics of bladder cancer. J Urol. 1994, 151: 545-560.PubMed
26.
go back to reference Knowles MA: Molecular genetics of bladder cancer. Br J Urol. 1995, 75: 57-66.PubMed Knowles MA: Molecular genetics of bladder cancer. Br J Urol. 1995, 75: 57-66.PubMed
27.
go back to reference Orlando V: Polycomb, epigenomes, and control of cell identity. Cell. 2003, 112: 599-606. 10.1016/S0092-8674(03)00157-0.CrossRefPubMed Orlando V: Polycomb, epigenomes, and control of cell identity. Cell. 2003, 112: 599-606. 10.1016/S0092-8674(03)00157-0.CrossRefPubMed
28.
go back to reference Jacobs JJ, Kieboom K, Marino S, Depinho RA, van Lohuizen M: The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature. 1999, 397: 164-168. 10.1038/16476.CrossRefPubMed Jacobs JJ, Kieboom K, Marino S, Depinho RA, van Lohuizen M: The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature. 1999, 397: 164-168. 10.1038/16476.CrossRefPubMed
29.
go back to reference Kang MK, Kim RH, Kim SJ, Yip FK, Shin KH, Dimri GP, Christensen R, Han T, Park NH: Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival. Br J Cancer. 2007, 96: 126-133. 10.1038/sj.bjc.6603529.CrossRefPubMed Kang MK, Kim RH, Kim SJ, Yip FK, Shin KH, Dimri GP, Christensen R, Han T, Park NH: Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival. Br J Cancer. 2007, 96: 126-133. 10.1038/sj.bjc.6603529.CrossRefPubMed
31.
go back to reference Dimri GP, Martinez JL, Jacobs JJ, Keblusek P, Itahana K, van Lohuizen M, Campisi J, Wazer DE, Band V: The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Res. 2002, 62 (16): 4736-4745.PubMed Dimri GP, Martinez JL, Jacobs JJ, Keblusek P, Itahana K, van Lohuizen M, Campisi J, Wazer DE, Band V: The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Res. 2002, 62 (16): 4736-4745.PubMed
32.
go back to reference Ball AJ, Levine F: Telomere-independent cellular senescence in human fetal cardiomyocytes. Aging Cell. 2005, 4: 21-30. 10.1111/j.1474-9728.2004.00137.x.CrossRefPubMed Ball AJ, Levine F: Telomere-independent cellular senescence in human fetal cardiomyocytes. Aging Cell. 2005, 4: 21-30. 10.1111/j.1474-9728.2004.00137.x.CrossRefPubMed
33.
go back to reference Reinisch CM, Uthman A, Erovic BM, Pammer J: Expression of BMI-1 in normal skin and inflammatory and neoplastic skin lesions. J Cutan Pathol. 2007, 34: 174-180. 10.1111/j.1600-0560.2006.00587.x.CrossRefPubMed Reinisch CM, Uthman A, Erovic BM, Pammer J: Expression of BMI-1 in normal skin and inflammatory and neoplastic skin lesions. J Cutan Pathol. 2007, 34: 174-180. 10.1111/j.1600-0560.2006.00587.x.CrossRefPubMed
34.
go back to reference Chang LL, Yeh WT, Yang SY, Wu WJ, Huang CH: Genetic alterations of p16INK4a and p14ARF genes in human bladder cancer. J Urol. 2003, 170: 595-600. 10.1097/01.ju.0000067626.37837.3e.CrossRefPubMed Chang LL, Yeh WT, Yang SY, Wu WJ, Huang CH: Genetic alterations of p16INK4a and p14ARF genes in human bladder cancer. J Urol. 2003, 170: 595-600. 10.1097/01.ju.0000067626.37837.3e.CrossRefPubMed
Metadata
Title
Expression of Bmi-1 is a prognostic marker in bladder cancer
Authors
Zi-Ke Qin
Jian-An Yang
Yun-lin Ye
Xing Zhang
Li-Hua Xu
Fang-Jian Zhou
Hui Han
Zuo-Wei Liu
Li-Bing Song
Mu-Sheng Zeng
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-61

Other articles of this Issue 1/2009

BMC Cancer 1/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine