Top

Published in:

Open Access 01-12-2018 | Research article

Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome

Authors: Katharina Grupp, Bianca Hofmann, Asad Kutup, Kai Bachmann, Dean Bogoevski, Nathaniel Melling, Faik Guntac Uzunoglu, Alexander Tarek El Gammal, Christina Koop, Ronald Simon, Stefan Steurer, Till Krech, Susanne Burdak-Rothkamm, Frank Jacobsen, Guido Sauter, Jakob Izbicki, Waldemar Wilczak

Published in: BMC Cancer | Issue 1/2018

Abstract

Background

RBM3 expression has been suggested as prognostic marker in several cancer types. The purpose of this study was to assess the prevalence and clinical significance of altered RBM3 expression in esophageal cancer.

Methods

RBM3 protein expression was measured by immunohistochemistry using tissue microarrays containing samples from 359 esophageal adenocarcinoma (EAC) and 254 esophageal squamous cell cancer (ESCC) patients with oncological follow-up data.

Results

While nuclear RBM3 expression was always high in benign esophageal epithelium, high RBM3 expression was only detectable in 66.4% of interpretable EACs and 59.3% of ESCCs. Decreased RBM3 expression was linked to a subset of EACs with advanced UICC stage and presence of distant metastasis (P = 0.0031 and P = 0.0024). In ESCC, decreased RBM3 expression was associated with advanced UICC stage, high tumor stage, and positive lymph node status (P = 0.0213, P = 0.0061, and P = 0.0192). However, RBM3 expression was largely unrelated to survival of patients with esophageal cancer (EAC: P = 0.212 and ESCC: P = 0.5992).

Conclusions

In summary, the present study shows that decreased RBM3 expression is associated with unfavourable esophageal cancer phenotype, but not significantly linked to patient prognosis.

Derry JMJ, 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. https://doi.org/10.1093/hmg/4.12.2307.CrossRefPubMed

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. https://doi.org/10.1242/jcs.01026.CrossRefPubMed

Al-Fageeh MB, Smales CM. Control and regulation of the cellular responses to cold shock: the responses in yeast and mammalian systems. Biochem J. 2006;397:247–59. https://doi.org/10.1042/BJ20060166.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1006/bbrc.1997.7059.CrossRefPubMed

Wright CF, Oswald BW, Dellis S. Vaccinia virus late transcription is activated in vitro by cellular heterogeneous nuclear ribonucleoproteins. J Biol Chem. 2001;276:40680–6. https://doi.org/10.1074/jbc.M102399200.CrossRefPubMed

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.CrossRef

Lleonart ME. A new generation of proto-oncogenes: cold-inducible RNA binding proteins. Biochim Biophys Acta. 1805;2010:43–52. https://doi.org/10.1016/j.bbcan.2009.11.001.CrossRef

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. https://doi.org/10.1038/onc.2008.97.CrossRefPubMedPubMedCentral

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. https://doi.org/10.1002/jcb.22114.CrossRefPubMedPubMedCentral

10.

Martínez-Arribas F, Agudo D, Pollán M, Gómez-Esquer F, Díaz-Gil G, Lucas R, Schneider J. Positive correlation between the expression of X-chromosome RBM genes (RBMX, RBM3, RBM10) and the proapoptotic Bax gene in human breast cancer. J Cell Biochem. 2006;97:1275–82. https://doi.org/10.1002/jcb.20725.CrossRefPubMed

11.

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. https://doi.org/10.1016/j.ejca.2013.12.003.CrossRefPubMed

12.

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;2:11. https://doi.org/10.1186/2050-7771-2-11.CrossRefPubMedPubMedCentral

13.

Olofsson S-E, Nodin B, Gaber A, Eberhard J, Uhlén M, Jirström K, Jerkeman M. 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. https://doi.org/10.1371/journal.pone.0121300.CrossRefPubMedPubMedCentral

14.

Boman K, Segersten U, Ahlgren G, Eberhard J, Uhlén M, Jirström K, Malmström P-U. Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer. BMC Urol. 2013;13:17. https://doi.org/10.1186/1471-2490-13-17.CrossRefPubMedPubMedCentral

15.

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. https://doi.org/10.1002/prca.201100020.CrossRefPubMed

16.

Jonsson L, Bergman J, Nodin B, Manjer J, Pontén F, Uhlén M, Jirström K. 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. https://doi.org/10.1186/1479-5876-9-114.CrossRefPubMedPubMedCentral

17.

Jonsson L, Gaber A, Ulmert D, Uhlén M, Bjartell A, Jirström K. High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression. Diagn Pathol. 2011;6:91. https://doi.org/10.1186/1746-1596-6-91.CrossRefPubMedPubMedCentral

18.

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. https://doi.org/10.1186/1479-5876-8-78.CrossRefPubMedPubMedCentral

19.

Jögi A, Brennan DJ, Rydén L, Magnusson K, Fernö M, Stål 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. https://doi.org/10.1038/modpathol.2009.124.CrossRefPubMed

20.

Mirlacher M, Simon R. Recipient block TMA technique. Methods Mol Biol. 2010;664:37–44. https://doi.org/10.1007/978-1-60761-806-5_4.CrossRefPubMed

21.

Melling N, Simon R, Mirlacher M, Izbicki JR, Stahl P, Terracciano LM, et al. RBM3 expression loss is associated with right-sided localization and poor prognosis in colorectal cancer. Histopathology. 2015. https://doi.org/10.1111/his.12726.CrossRef

22.

Kita H, Carmichael J, Swartz J, Muro S, Wyttenbach A, Matsubara K, et al. Modulation of polyglutamine-induced cell death by genes identified by expression profiling. Hum Mol Genet. 2002;11:2279–87.CrossRef

23.

Wellmann S, Truss M, Bruder E, Tornillo L, Zelmer A, Seeger K, Bührer C. The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death. Pediatr Res. 2010;67:35–41. https://doi.org/10.1203/PDR.0b013e3181c13326.CrossRefPubMed

24.

Baldi A, Battista T, de Luca A, Santini D, Rossiello L, Baldi F, et al. Identification of genes down-regulated during melanoma progression: a cDNA array study. Exp Dermatol. 2003;12:213–8.CrossRef

25.

Kim R, Inoue H, Toge T. Bax is an important determinant for radiation sensitivity in esophageal carcinoma cells. Int J Mol Med. 2004;14:697–706.PubMed

26.

Mandard AM, Hainaut P, Hollstein M. Genetic steps in the development of squamous cell carcinoma of the esophagus. Mutat Res. 2000;462:335–42.CrossRef

27.

Shimizu M, Ban S, Odze RD. Squamous dysplasia and other precursor lesions related to esophageal squamous cell carcinoma. Gastroenterol Clin N Am. 2007;36:797–811, v-vi. https://doi.org/10.1016/j.gtc.2007.08.005.CrossRef

28.

Toh Y, Oki E, Ohgaki K, Sakamoto Y, Ito S, Egashira A, et al. Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis. Int J Clin Oncol. 2010;15:135–44. https://doi.org/10.1007/s10147-010-0057-6.CrossRefPubMed

29.

Hollstein MC, Peri L, Mandard AM, Welsh JA, Montesano R, Metcalf RA, et al. Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations. Cancer Res. 1991;51:4102–6.PubMed

30.

Yazbeck R, Jaenisch SE, Watson DI. From blood to breath: new horizons for esophageal cancer biomarkers. World J Gastroenterol. 2016;22:10077–83. https://doi.org/10.3748/wjg.v22.i46.10077.CrossRefPubMedPubMedCentral

31.

Li J, Lenferink AEG, Deng Y, Collins C, Cui Q, Purisima EO, et al. Identification of high-quality cancer prognostic markers and metastasis network modules. Nat Commun. 2010;1:34. https://doi.org/10.1038/ncomms1033.CrossRefPubMed

32.

Rubin MA, Dunn R, Strawderman M, Pienta KJ. Tissue microarray sampling strategy for prostate cancer biomarker analysis. Am J Surg Pathol. 2002;26:312–9.CrossRef

33.

Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Köchli OR, et al. Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol. 2001;159:2249–56. https://doi.org/10.1016/S0002-9440(10)63075-1.CrossRefPubMedPubMedCentral

34.

Tennstedt P, Köster P, Brüchmann A, Mirlacher M, Haese A, Steuber T, et al. The impact of the number of cores on tissue microarray studies investigating prostate cancer biomarkers. Int J Oncol. 2012;40:261–8. https://doi.org/10.3892/ijo.2011.1216.CrossRefPubMed

Title: Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome
Authors: Katharina Grupp
Bianca Hofmann
Asad Kutup
Kai Bachmann
Dean Bogoevski
Nathaniel Melling
Faik Guntac Uzunoglu
Alexander Tarek El Gammal
Christina Koop
Ronald Simon
Stefan Steurer
Till Krech
Susanne Burdak-Rothkamm
Frank Jacobsen
Guido Sauter
Jakob Izbicki
Waldemar Wilczak
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-5032-z

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

RETRACTED ARTICLE: Ras-ERK1/2 signaling contributes to the development of colorectal cancer via regulating H3K9ac

Tumor necrosis as a prognostic variable for the clinical outcome in patients with renal cell carcinoma: a systematic review and meta-analysis

Pancreatic adenocarcinoma: insights into patterns of recurrence and disease behavior

Detection of circulating tumor cells in patients with pituitary tumors

Androgen deprivation therapy during and after post-prostatectomy radiotherapy in patients with prostate cancer: a case control study

Thoracic injection of low-dose interleukin-2 as an adjuvant therapy improves the control of the malignant pleural effusions: a systematic review and meta-analysis base on Chinese patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer