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Open Access 01-12-2015 | Research

Evaluation of RNA-binding motif protein 3 expression in urothelial carcinoma of the bladder: an immunohistochemical study

Authors: Livia Florianova, Bin Xu, Samer Traboulsi, Hazem Elmansi, Simon Tanguay, Armen Aprikian, Wassim Kassouf, Fadi Brimo

Published in: World Journal of Surgical Oncology | Issue 1/2015

Abstract

Background

RNA-binding motif protein 3 (RBM3), involved in cell survival, has paradoxically been linked to both oncogenesis as well as an increased survival in several cancers, including urothelial carcinoma (UCA).

Methods

The putative prognostic role of RBM3 was studied using cystectomy specimens with 152 invasive UCA with 35 matched metastases, 65 carcinomas in situ (CIS), 22 high-grade papillary UCAs (PAP), and 112 benign urothelium cases.

Results

The H-score (HS, staining intensity × % of positive cells) was used for RBM3 immunoexpression. CIS showed the highest HS (mean = 140) followed by benign urothelium (mean = 97). Metastases showed higher HS than primary invasive UCA (P ≤ 0.0001), and high HS was associated with a lower pT stage (P ≤ 0.0001) and a trend toward the absence of lymphovascular invasion (LVI, P = 0.09), but not pN stage (P = 0.35) and surgical margin status (P = 0.81). Univariate analysis (UVA) of disease recurrence only showed an association between pN stage and LVI (P = 0.005 and 0.03, respectively). On UVA of mortality, pT stage was strongly associated with death (P = 0.01) while pN stage, LVI, surgical margin status, and HS were not. Multivariate analysis confirmed the lack of HS association with recurrence (P = 0.08) and death (P = 0.32).

Conclusions

Stronger RBM3 immunoexpression correlated with lower stage tumors and a diminished risk for LVI. However, RBM3 does not seem to carry a prognostic significance for clinical outcome (recurrence and mortality). The exact prognostic role of RBM3 in UCA is yet to be determined.

Sutherland LC, Rintala-Maki ND, White RD, Morin CD. RNA binding motif (RBM) proteins: a novel family of apoptosis modulators? J Cell Biochem. 2005;94:5–24.CrossRefPubMed

Burd CG, Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science. 1994;265:615–21.CrossRefPubMed

Lleonart ME. A new generation of proto-oncogenes: cold-inducible RNA binding proteins. Biochim Biophys Acta. 2010;1805:43–52.

Wellmann S, Truss M, Bruder E, Tornillo L, Zelmer A, Seeger K, et al. The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death. Pediatr Res. 2010;67:35–41.

Wellmann S, Bührer C, Moderegger E, Zelmer A, Kirschner R, Koehne P, et al. Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism. J Cell Sci. 2004;117:1785–94.

Danno S, Nishiyama H, Higashitsuji H, Yokoi H, Xue JH, Itoh K, et al. 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;236:804–7.

Derry JM, Kerns JA, Francke U. RBM3, a novel human gene in Xp11.23 with a putative RNA-binding domain. Hum Mol Genet. 1995;4:2307–11.CrossRefPubMed

Chappell SA, Owens GC, Mauro VP. A 5’ leader of Rbm3, a cold stress-induced mRNA, mediates internal initiation of translation with increased efficiency under conditions of mild hypothermia. J Biol Chem. 2001;276:36917–22.CrossRefPubMed

De Leeuw F, Zhang T, Wauquier C, Huez G, Kruys V, Gueydan C. The cold-inducible RNA-binding protein migrates from the nucleus to cytoplasmic stress granules by a methylation-dependent mechanism and acts as a translational repressor. Exp Cell Res. 2007;313:4130–44.

10.

Neutelings T, Lambert CA, Nusgens BV, Colige AC. Effects of mild cold shock (25 °C) followed by warming up at 37 °C on the cellular stress response. PLoS One. 2013;8:e69687.PubMedCentralCrossRefPubMed

11.

Dresios J, Aschrafi A, Owens GC, Vanderklish PW, Edelman GM, Mauro VP. Cold stress-induced protein Rbm3 binds 60S ribosomal subunits, alters microRNA levels, and enhances global protein synthesis. Proc Natl Acad Sci USA. 2005;102:1865–70.

12.

Sureban SM, Ramalingam S, Natarajan G, May R, Subramaniam D, Bishnupuri KS, et al. Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe. Oncogene. 2008;27:4544–56.

13.

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;107:179–88.PubMedCentralCrossRefPubMed

14.

Shaikhibrahim Z, Lindstrot A, Ochsenfahrt J, Fuchs K, Wernert N. Epigenetics-related genes in prostate cancer: expression profile in prostate cancer tissues, androgen-sensitive and -insensitive cell lines. Int J Mol Med. 2013;31:21–5.

15.

Zhang HT, Zhang ZW, Xue JH, Kong HB, Liu AJ, Li SC, et al. Differential expression of the RNA-binding motif protein 3 in human astrocytoma. Chin Med J (Engl). 2013;126:1948–852.

16.

Grupp K, Wilking J, Prien K, Hube-Magg C, Sirma H, Simon R, et al. High RNA-binding motif protein 3 expression is an independent prognostic marker in operated prostate cancer and tightly linked to ERG activation and PTEN deletions. Eur J Cancer. 2014;50:852–61.

17.

Zeng Y, Wodzenski D, Gao D, Shiraishi T, Terada N, Li Y, et al. Stress-response protein RBM3 attenuates the stem-like properties of prostate cancer cells by interfering with CD44 variant splicing. Cancer Res. 2013;73:4123–33.

18.

Hjelm B, Brennan DJ, Zendehrokh N, Eberhard J, Nodin B, Gaber A, et al. High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer. Proteomics Clin Appl. 2011;5:624–35.

19.

Jonsson L, Bergman J, Nodin B, Manjer J, Ponten F, Uhlen M, et al. Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmö Diet and Cancer Study. J Transl Med. 2011;9:114–22.

20.

Nodin B, Fridberg M, Jonsson L, Bergman J, Uhlén M, Jirström K, et al. High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma. Diagn Pathol. 2012;7:82–91.

21.

Jögi A, Brennan DJ, Rydén L, Magnusson K, Ferno M, Stal O, et al. Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Mod Pathol. 2009;22:1564–74.

22.

Jonsson L, Hedner C, Gaber A, Korkocic D, Nodin B, Uhlén M, et al. High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death. Biomark Res. 2014;17:11–21.

23.

Ehlén A, Brennan DJ, Nodin B, O’Connor DP, Eberhard J, Alvarado-Kristensson 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;8:78–89.

24.

Ehlén Å, Nodin B, Rexhepaj E, Brändstedt J, Uhlén M, Alvarado-Kristensson M, et al. RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer. Transl Oncol. 2011;4:212–21.

25.

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;6:91–6.PubMedCentralCrossRefPubMed

26.

Boman K, Segersten U, Ahlgren G, Eberhard J, Uhlén M, Jirström K, et al. Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer. BMC Urol. 2013;13:17–24.

27.

Olofsson SE, Nodin B, Gaber A, Eberhard J, Uhlén M, Jirström K, et al. Low RBM3 protein expression correlates with clinical stage, prognostic classification and increased risk of treatment failure in testicular non-seminomatous germ cell cancer. PLoS One. 2015;10:e0121300.

Title: Evaluation of RNA-binding motif protein 3 expression in urothelial carcinoma of the bladder: an immunohistochemical study
Authors: Livia Florianova
Bin Xu
Samer Traboulsi
Hazem Elmansi
Simon Tanguay
Armen Aprikian
Wassim Kassouf
Fadi Brimo
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2015
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/s12957-015-0730-3

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Springer Medicine

Evaluation of RNA-binding motif protein 3 expression in urothelial carcinoma of the bladder: an immunohistochemical study

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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