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Diagnostic Pathology

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Open Access 01-12-2011 | Short report

High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

Authors: Liv Jonsson, Alexander Gaber, David Ulmert, Mathias Uhlén, Anders Bjartell, Karin Jirström

Published in: Diagnostic Pathology | Issue 1/2011

Abstract

Background

High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer.

Findings

Immunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR) (HR 0.56, 95% CI: 0.34-0.93, p = 0.024) and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p = 0.021). These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression).

Conclusion

Our results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.

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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61 (2): 69-90. 10.3322/caac.20107.CrossRefPubMed

Ferlay J, Parkin DM, Steliarova-Foucher E: Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010, 46 (4): 765-781. 10.1016/j.ejca.2009.12.014.CrossRefPubMed

Bill-Axelson A, Holmberg L, Ruutu M, Garmo H, Stark JR, Busch C, Nordling S, Haggman M, Andersson SO, Bratell S, et al.: Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011, 364 (18): 1708-1717. 10.1056/NEJMoa1011967.CrossRefPubMed

Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC: Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999, 281 (17): 1591-1597. 10.1001/jama.281.17.1591.CrossRefPubMed

Bjartell A, Montironi R, Berney DM, Egevad L: Tumour markers in prostate cancer II: diagnostic and prognostic cellular biomarkers. Acta Oncol. 2011, 50 (Suppl 1): 76-84.CrossRefPubMed

Shariat SF, Semjonow A, Lilja H, Savage C, Vickers AJ, Bjartell A: Tumor markers in prostate cancer I: blood-based markers. Acta Oncol. 2011, 50 (Suppl 1): 61-75.PubMedCentralCrossRefPubMed

Danno S, Nishiyama H, Higashitsuji H, Yokoi H, Xue JH, Itoh K, Matsuda T, Fujita J: Increased transcript level of RBM3, a member of the glycine-rich RNA-binding protein family, in human cells in response to cold stress. Biochem Biophys Res Commun. 1997, 236 (3): 804-807. 10.1006/bbrc.1997.7059.CrossRefPubMed

Lleonart ME: A new generation of proto-oncogenes: cold-inducible RNA binding proteins. Biochim Biophys Acta. 2010, 1805 (1): 43-52.PubMed

Sureban SM, Ramalingam S, Natarajan G, May R, Subramaniam D, Bishnupuri KS, Morrison AR, Dieckgraefe BK, Brackett DJ, Postier RG, et al.: Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe. Oncogene. 2008, 27 (33): 4544-4556. 10.1038/onc.2008.97.PubMedCentralCrossRefPubMed

10.

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

11.

Jogi A, Brennan DJ, Ryden L, Magnusson K, Ferno M, Stal O, Borgquist S, Uhlen M, Landberg G, Pahlman S, et al.: Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Mod Pathol. 2009, 22 (12): 1564-1574. 10.1038/modpathol.2009.124.CrossRefPubMed

12.

Uhlen M, Bjorling E, Agaton C, Szigyarto CA, Amini B, Andersen E, Andersson AC, Angelidou P, Asplund A, Asplund C, et al.: A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics. 2005, 4 (12): 1920-1932. 10.1074/mcp.M500279-MCP200.CrossRefPubMed

13.

Bjorling E, Lindskog C, Oksvold P, Linne J, Kampf C, Hober S, Uhlen M, Ponten F: A web-based tool for in silico biomarker discovery based on tissue-specific protein profiles in normal and cancer tissues. Mol Cell Proteomics. 2008, 7 (5): 825-844. 10.1074/mcp.M700411-MCP200.CrossRefPubMed

14.

Ponten F, Jirstrom K, Uhlen M: The Human Protein Atlas--a tool for pathology. J Pathol. 2008, 216 (4): 387-393. 10.1002/path.2440.CrossRefPubMed

15.

Ehlen A, Brennan DJ, Nodin B, O'Connor DP, Eberhard J, Alvarado-Kristensson M, Jeffrey IB, Manjer J, Brandstedt J, Uhlen M, et al.: 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.PubMedCentralCrossRefPubMed

16.

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 (1): 114-10.1186/1479-5876-9-114.PubMedCentralCrossRefPubMed

17.

Ehlen O, 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. Transl Oncol. 2011, 4 (4): 212-221.PubMedCentralCrossRefPubMed

18.

Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, et al.: Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol. 2007, 177 (2): 540-545. 10.1016/j.juro.2006.10.097.CrossRefPubMed

19.

Zeng Y, Kulkarni P, Inoue T, Getzenberg RH: Down-regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity. J Cell Biochem. 2009, 107 (1): 179-188. 10.1002/jcb.22114.PubMedCentralCrossRefPubMed

20.

Popat S, Hubner R, Houlston RS: Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005, 23 (3): 609-618.CrossRefPubMed

21.

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

22.

Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, et al.: DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005, 434 (7035): 864-870. 10.1038/nature03482.CrossRefPubMed

23.

Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, Venere M, Ditullio RA, Kastrinakis NG, Levy B, et al.: Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature. 2005, 434 (7035): 907-913. 10.1038/nature03485.CrossRefPubMed

Title: High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression
Authors: Liv Jonsson
Alexander Gaber
David Ulmert
Mathias Uhlén
Anders Bjartell
Karin Jirström
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2011
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/1746-1596-6-91

Keynote webinar | Spotlight on medication adherence

Springer Medicine

High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

Abstract

Background

Findings

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Findings

Conclusion

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