Skip to main content
Top
Published in: BMC Urology 1/2013

Open Access 01-12-2013 | Research article

Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer

Authors: Karolina Boman, Ulrika Segersten, Göran Ahlgren, Jakob Eberhard, Mathias Uhlén, Karin Jirström, Per-Uno Malmström

Published in: BMC Urology | Issue 1/2013

Login to get access

Abstract

Background

Low nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to be associated with poor prognosis in several cancer forms e.g. breast, ovarian, colorectal, prostate cancer and malignant melanoma. The aim of this study was to examine the prognostic impact of RBM3 expression in urinary bladder cancer.

Methods

Immunohistochemical RBM3 expression was examined in tumours from 343 patients with urothelial bladder cancer. Chi-square and Spearman’s correlation tests were applied to explore associations between RBM3 expression and clinicopathological characteristics. The impact of RBM3 expression on disease-specific survival (DSS), 5-year overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analysis and Cox proportional hazards modelling.

Results

Reduced nuclear RBM3 expression was significantly associated with more advanced tumour (T) stage (p <0.001) and high grade tumours (p=0.004). Negative RBM3 expression was associated with a significantly shorter DSS (HR=2.55; 95% CI 1.68-3.86)) and 5-year OS (HR=2.10; 95% CI 1.56-2.82), also in multivariable analysis (HR=1.65; 95% CI 1.07-2.53 for DSS and HR=1.54; 95% CI 1.13-2.10 for 5-year OS). In patients with Ta and T1 tumours expressing reduced RBM3 levels, Kaplan-Meier analysis revealed a significantly shorter PFS (p=0.048) and 5-year OS (p=0.006).

Conclusion

Loss of RBM3 expression is associated with clinically more aggressive tumours and an independent factor of poor prognosis in patients with urothelial bladder cancer and a potentially useful biomarker for treatment stratification and surveillance of disease progression.
Appendix
Available only for authorised users
Literature
1.
go back to reference Raghavan D, Shipley WU, Garnick MB, Russell PJ, Richie JP: Biology and management of bladder cancer. N Engl J Med. 1990, 322 (16): 1129-1138. 10.1056/NEJM199004193221607.CrossRefPubMed Raghavan D, Shipley WU, Garnick MB, Russell PJ, Richie JP: Biology and management of bladder cancer. N Engl J Med. 1990, 322 (16): 1129-1138. 10.1056/NEJM199004193221607.CrossRefPubMed
2.
go back to reference Masood S, Sriprasad S, Palmer JH, Mufti GR: T1G3 bladder cancer–indications for early cystectomy. Int Urol Nephrol. 2004, 36 (1): 41-44.CrossRefPubMed Masood S, Sriprasad S, Palmer JH, Mufti GR: T1G3 bladder cancer–indications for early cystectomy. Int Urol Nephrol. 2004, 36 (1): 41-44.CrossRefPubMed
3.
go back to reference Lebret T, Watson RW, Molinie V, Poulain JE, O'Neill A, Fitzpatrick JM, Botto H: HSP90 expression: a new predictive factor for BCG response in stage Ta-T1 grade 3 bladder tumours. Eur Urol. 2007, 51 (1): 161-166. 10.1016/j.eururo.2006.06.006. discussion 166–167CrossRefPubMed Lebret T, Watson RW, Molinie V, Poulain JE, O'Neill A, Fitzpatrick JM, Botto H: HSP90 expression: a new predictive factor for BCG response in stage Ta-T1 grade 3 bladder tumours. Eur Urol. 2007, 51 (1): 161-166. 10.1016/j.eururo.2006.06.006. discussion 166–167CrossRefPubMed
4.
go back to reference Sternberg CN: The treatment of advanced bladder cancer. Ann Oncol. 1995, 6 (2): 113-126.PubMed Sternberg CN: The treatment of advanced bladder cancer. Ann Oncol. 1995, 6 (2): 113-126.PubMed
5.
go back to reference Soloway MS, Lopez AE, Patel J, Lu Y: Results of radical cystectomy for transitional cell carcinoma of the bladder and the effect of chemotherapy. Cancer. 1994, 73 (7): 1926-1931. 10.1002/1097-0142(19940401)73:7<1926::AID-CNCR2820730725>3.0.CO;2-Q.CrossRefPubMed Soloway MS, Lopez AE, Patel J, Lu Y: Results of radical cystectomy for transitional cell carcinoma of the bladder and the effect of chemotherapy. Cancer. 1994, 73 (7): 1926-1931. 10.1002/1097-0142(19940401)73:7<1926::AID-CNCR2820730725>3.0.CO;2-Q.CrossRefPubMed
6.
go back to reference Hjelm B, Brennan DJ, Zendehrokh N, Eberhard J, Nodin B, Gaber A, Ponten F, Johannesson H, Smaragdi K, Frantz C: High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer. Proteomics Clin Appl. 2011, 5 (11–12): 624-635.CrossRefPubMed Hjelm B, Brennan DJ, Zendehrokh N, Eberhard J, Nodin B, Gaber A, Ponten F, Johannesson H, Smaragdi K, Frantz C: High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer. Proteomics Clin Appl. 2011, 5 (11–12): 624-635.CrossRefPubMed
7.
go back to reference Jogi A, Brennan DJ, Ryden L, Magnusson K, Ferno M, Stal O, Borgquist S, Uhlen M, Landberg G, Pahlman S: Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 2009, 22 (12): 1564-1574. 10.1038/modpathol.2009.124.CrossRef Jogi A, Brennan DJ, Ryden L, Magnusson K, Ferno M, Stal O, Borgquist S, Uhlen M, Landberg G, Pahlman S: Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 2009, 22 (12): 1564-1574. 10.1038/modpathol.2009.124.CrossRef
8.
go back to reference Jonsson L, Bergman J, Nodin B, Manjer J, Ponten F, Uhlen M, Jirstrom K: Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmo Diet and Cancer Study. J Transl Med. 2011, 9: 114-10.1186/1479-5876-9-114.CrossRefPubMedPubMedCentral Jonsson L, Bergman J, Nodin B, Manjer J, Ponten F, Uhlen M, Jirstrom K: Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmo Diet and Cancer Study. J Transl Med. 2011, 9: 114-10.1186/1479-5876-9-114.CrossRefPubMedPubMedCentral
9.
go back to reference Jonsson L, Gaber A, Ulmert D, Uhlen M, Bjartell A, Jirstrom K: High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression. Diagn Pathol. 2011, 6: 91-10.1186/1746-1596-6-91.CrossRefPubMedPubMedCentral Jonsson L, Gaber A, Ulmert D, Uhlen M, Bjartell A, Jirstrom K: High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression. Diagn Pathol. 2011, 6: 91-10.1186/1746-1596-6-91.CrossRefPubMedPubMedCentral
10.
go back to reference Ehlen A, Brennan DJ, Nodin B, O'Connor DP, Eberhard J, Alvarado-Kristensson M, Jeffrey IB, Manjer J, Brandstedt J, Uhlen M: Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer. J Transl Med. 2010, 8: 78-10.1186/1479-5876-8-78.CrossRefPubMedPubMedCentral Ehlen A, Brennan DJ, Nodin B, O'Connor DP, Eberhard J, Alvarado-Kristensson M, Jeffrey IB, Manjer J, Brandstedt J, Uhlen M: Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer. J Transl Med. 2010, 8: 78-10.1186/1479-5876-8-78.CrossRefPubMedPubMedCentral
11.
go back to reference Ehlen A, Nodin B, Rexhepaj E, Brandstedt J, Uhlen M, Alvarado-Kristensson M, Ponten F, Brennan DJ, Jirstrom K: RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer. Translational oncology. 2011, 4 (4): 212-221.CrossRefPubMedPubMedCentral Ehlen A, Nodin B, Rexhepaj E, Brandstedt J, Uhlen M, Alvarado-Kristensson M, Ponten F, Brennan DJ, Jirstrom K: RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer. Translational oncology. 2011, 4 (4): 212-221.CrossRefPubMedPubMedCentral
12.
go back to reference Sauter GAF, Amin MB: Noninvasive urothelial neoplasias; WHO classification of noninvasive papillary urothelial tumours. A World Health Organization Classification of Tumours Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Edited by: In Elbe JN EJ, Sesterhenn I. 2004, Lyon: IARCC Sauter GAF, Amin MB: Noninvasive urothelial neoplasias; WHO classification of noninvasive papillary urothelial tumours. A World Health Organization Classification of Tumours Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Edited by: In Elbe JN EJ, Sesterhenn I. 2004, Lyon: IARCC
13.
go back to reference Sureban SM, Ramalingam S, Natarajan G, May R, Subramaniam D, Bishnupuri KS, Morrison AR, Dieckgraefe BK, Brackett DJ, Postier RG: Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe. Oncogene. 2008, 27 (33): 4544-4556. 10.1038/onc.2008.97.CrossRefPubMedPubMedCentral Sureban SM, Ramalingam S, Natarajan G, May R, Subramaniam D, Bishnupuri KS, Morrison AR, Dieckgraefe BK, Brackett DJ, Postier RG: Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe. Oncogene. 2008, 27 (33): 4544-4556. 10.1038/onc.2008.97.CrossRefPubMedPubMedCentral
14.
go back to reference Wellmann S, Truss M, Bruder E, Tornillo L, Zelmer A, Seeger K, Buhrer C: The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death. Pediatr Res. 2010, 67 (1): 35-41. 10.1203/PDR.0b013e3181c13326.CrossRefPubMed Wellmann S, Truss M, Bruder E, Tornillo L, Zelmer A, Seeger K, Buhrer C: The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death. Pediatr Res. 2010, 67 (1): 35-41. 10.1203/PDR.0b013e3181c13326.CrossRefPubMed
15.
go back to reference Bartkova J, Rajpert-De Meyts E, Skakkebaek NE, Lukas J, Bartek J: DNA damage response in human testes and testicular germ cell tumours: biology and implications for therapy. Int J Androl. 2007, 30 (4): 282-291. 10.1111/j.1365-2605.2007.00772.x. discussion 291CrossRefPubMed Bartkova J, Rajpert-De Meyts E, Skakkebaek NE, Lukas J, Bartek J: DNA damage response in human testes and testicular germ cell tumours: biology and implications for therapy. Int J Androl. 2007, 30 (4): 282-291. 10.1111/j.1365-2605.2007.00772.x. discussion 291CrossRefPubMed
16.
go back to reference Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C: DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005, 434 (7035): 864-870. 10.1038/nature03482.CrossRefPubMed Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C: DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005, 434 (7035): 864-870. 10.1038/nature03482.CrossRefPubMed
17.
go back to reference Loehrer PJ, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, Raghavan D, Stuart-Harris R, Sarosdy MF, Lowe BA: A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992, 10 (7): 1066-1073.PubMed Loehrer PJ, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, Raghavan D, Stuart-Harris R, Sarosdy MF, Lowe BA: A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992, 10 (7): 1066-1073.PubMed
18.
go back to reference Meeks JJ, Bellmunt J, Bochner BH, Clarke NW, Daneshmand S, Galsky MD, Hahn NM, Lerner SP, Mason M, Powles T: A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2012, 62 (3): 523-533. 10.1016/j.eururo.2012.05.048.CrossRefPubMed Meeks JJ, Bellmunt J, Bochner BH, Clarke NW, Daneshmand S, Galsky MD, Hahn NM, Lerner SP, Mason M, Powles T: A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2012, 62 (3): 523-533. 10.1016/j.eururo.2012.05.048.CrossRefPubMed
19.
go back to reference Sternberg CN, Bellmunt J, Sonpavde G, Siefker-Radtke AO, Stadler WM, Bajorin DF, Dreicer R, George DJ, Milowsky MI, Theodorescu D: ICUD-EAU International Consultation on Bladder Cancer 2012: chemotherapy for urothelial carcinoma-neoadjuvant and adjuvant settings. Eur Urol. 2013, 63 (1): 58-66. 10.1016/j.eururo.2012.08.010.CrossRefPubMed Sternberg CN, Bellmunt J, Sonpavde G, Siefker-Radtke AO, Stadler WM, Bajorin DF, Dreicer R, George DJ, Milowsky MI, Theodorescu D: ICUD-EAU International Consultation on Bladder Cancer 2012: chemotherapy for urothelial carcinoma-neoadjuvant and adjuvant settings. Eur Urol. 2013, 63 (1): 58-66. 10.1016/j.eururo.2012.08.010.CrossRefPubMed
20.
go back to reference von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM: Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000, 18 (17): 3068-3077.PubMed von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM: Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000, 18 (17): 3068-3077.PubMed
21.
go back to reference Sievert KD, Amend B, Nagele U, Schilling D, Bedke J, Horstmann M, Hennenlotter J, Kruck S, Stenzl A: Economic aspects of bladder cancer: what are the benefits and costs?. World J Urol. 2009, 27 (3): 295-300. 10.1007/s00345-009-0395-z.CrossRefPubMedPubMedCentral Sievert KD, Amend B, Nagele U, Schilling D, Bedke J, Horstmann M, Hennenlotter J, Kruck S, Stenzl A: Economic aspects of bladder cancer: what are the benefits and costs?. World J Urol. 2009, 27 (3): 295-300. 10.1007/s00345-009-0395-z.CrossRefPubMedPubMedCentral
22.
go back to reference Raab SS, Grzybicki DM, Vrbin CM, Geisinger KR: Urine cytology discrepancies: frequency, causes, and outcomes. Am J Clin Pathol. 2007, 127 (6): 946-953. 10.1309/XUVXFXMFPL7TELCE.CrossRefPubMed Raab SS, Grzybicki DM, Vrbin CM, Geisinger KR: Urine cytology discrepancies: frequency, causes, and outcomes. Am J Clin Pathol. 2007, 127 (6): 946-953. 10.1309/XUVXFXMFPL7TELCE.CrossRefPubMed
Metadata
Title
Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer
Authors
Karolina Boman
Ulrika Segersten
Göran Ahlgren
Jakob Eberhard
Mathias Uhlén
Karin Jirström
Per-Uno Malmström
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2013
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/1471-2490-13-17

Other articles of this Issue 1/2013

BMC Urology 1/2013 Go to the issue