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Open Access 01-12-2013 | Research article

Low expression of the X-linked ribosomal protein S4 in human serous epithelial ovarian cancer is associated with a poor prognosis

Authors: Serges P Tsofack, Liliane Meunier, Lilia Sanchez, Jason Madore, Diane Provencher, Anne-Marie Mes-Masson, Michel Lebel

Published in: BMC Cancer | Issue 1/2013

Abstract

Background

The X-linked ribosomal protein S4 (RPS4X), which is involved in cellular translation and proliferation, has previously been identified as a partner of the overexpressed multifunctional protein YB-1 in several breast cancer cells. Depletion of RPS4X results in consistent resistance to cisplatin in such cell lines.

Methods

As platinum-based chemotherapy is a standard first line therapy used to treat patients with ovarian cancer, we evaluated the prognostic value of RPS4X and YB-1 at the protein level in specimen from 192 high-grade serous epithelial ovarian cancer patients.

Results

Immunohistochemistry studies indicated that high expression of RPS4X was associated with a lower risk of death and later disease progression (HR = 0.713, P = 0.001 and HR = 0.761, P = 0.001, respectively) as compared to low expression of RPS4X. In contrast, YB-1 was not significantly associated with either recurrence or survival time in this cohort. Finally, the depletion of RPS4X with different siRNAs in two different ovarian cancer cell lines reduced their proliferative growth rate but more importantly increased their resistance to cisplatin.

Conclusion

Altogether, these results suggest that the levels of RPS4X could be a good indicator for resistance to platinum-based therapy and a prognostic marker for ovarian cancer. Our study also showed that RPS4X is an independent prognostic factor in patients with serous epithelial ovarian cancer.

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NIH Consensus Conference: Ovarian cancer. Screening, treatment, and follow-up. NIH Consensus Development Panel on Ovarian Cancer. JAMA. 1995, 273 (6): 491-497. 10.1001/jama.1995.03520300065039.CrossRef

DiSaia PJ, Bloss JD: Treatment of ovarian cancer: new strategies. Gynecol Oncol. 2003, 90 (2 Pt 2): S24-S32.CrossRefPubMed

Greenlee RT, Hill-Harmon MB, Murray T, Thun M: Cancer statistics, 2001. CA Cancer J Clin. 2001, 51 (1): 15-36. 10.3322/canjclin.51.1.15.CrossRefPubMed

Marsh S: Pharmacogenomics of taxane/platinum therapy in ovarian cancer. Int J Gynecol Cancer. 2009, 19 (Suppl 2): S30-S34. 10.1111/IGC.0b013e3181c10513.CrossRefPubMed

Kartalou M, Essigmann JM: Mechanisms of resistance to cisplatin. Mutat Res. 2001, 478 (1–2): 23-43.CrossRefPubMed

Yahata H, Kobayashi H, Kamura T, Amada S, Hirakawa T, Kohno K, Kuwano M, Nakano H: Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer. J Cancer Res Clin Oncol. 2002, 128 (11): 621-626. 10.1007/s00432-002-0386-6.CrossRefPubMed

Oda Y, Ohishi Y, Basaki Y, Kobayashi H, Hirakawa T, Wake N, Ono M, Nishio K, Kuwano M, Tsuneyoshi M: Prognostic implications of the nuclear localization of Y-box-binding protein-1 and CXCR4 expression in ovarian cancer: their correlation with activated Akt, LRP/MVP and P-glycoprotein expression. Cancer Sci. 2007, 98 (7): 1020-1026. 10.1111/j.1349-7006.2007.00492.x.CrossRefPubMed

Swamynathan SK, Nambiar A, Guntaka RV: Role of single-stranded DNA regions and Y-box proteins in transcriptional regulation of viral and cellular genes. FASEB J. 1998, 12 (7): 515-522.PubMed

Stickeler E, Fraser SD, Honig A, Chen AL, Berget SM, Cooper TA: The RNA binding protein YB-1 binds A/C-rich exon enhancers and stimulates splicing of the CD44 alternative exon v4. EMBO J. 2001, 20 (14): 3821-3830. 10.1093/emboj/20.14.3821.CrossRefPubMedPubMedCentral

10.

Ashizuka M, Fukuda T, Nakamura T, Shirasuna K, Iwai K, Izumi H, Kohno K, Kuwano M, Uchiumi T: Novel translational control through an iron-responsive element by interaction of multifunctional protein YB-1 and IRP2. Mol Cell Biol. 2002, 22 (18): 6375-6383. 10.1128/MCB.22.18.6375-6383.2002.CrossRefPubMedPubMedCentral

11.

Evdokimova V, Ruzanov P, Anglesio MS, Sorokin AV, Ovchinnikov LP, Buckley J, Triche TJ, Sonenberg N, Sorensen PH: Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species. Mol Cell Biol. 2006, 26 (1): 277-292. 10.1128/MCB.26.1.277-292.2006.CrossRefPubMedPubMedCentral

12.

Ise T, Nagatani G, Imamura T, Kato K, Takano H, Nomoto M, Izumi H, Ohmori H, Okamoto T, Ohga T, et al: Transcription factor Y-box binding protein 1 binds preferentially to cisplatin-modified DNA and interacts with proliferating cell nuclear antigen. Cancer Res. 1999, 59 (2): 342-346.PubMed

13.

Pestryakov P, Zharkov DO, Grin I, Fomina EE, Kim ER, Hamon L, Eliseeva IA, Petruseva IO, Curmi PA, Ovchinnikov LP, et al: Effect of the multifunctional proteins RPA, YB-1, and XPC repair factor on AP site cleavage by DNA glycosylase NEIL1. J Mol Recognit. 2012, 25 (4): 224-233. 10.1002/jmr.2182.CrossRefPubMed

14.

Guay D, Garand C, Reddy S, Schmutte C, Lebel M: The human endonuclease III enzyme is a relevant target to potentiate cisplatin cytotoxicity in Y-box-binding protein-1 overexpressing tumor cells. Cancer Sci. 2008, 99 (4): 762-769. 10.1111/j.1349-7006.2008.00739.x.CrossRefPubMed

15.

Garand C, Guay D, Sereduk C, Chow D, Tsofack SP, Langlois M, Perreault E, Yin HH, Lebel M: An integrative approach to identify YB-1-interacting proteins required for cisplatin resistance in MCF7 and MDA-MB-231 breast cancer cells. Cancer Sci. 2011, 102 (7): 1410-1417. 10.1111/j.1349-7006.2011.01948.x.CrossRefPubMed

16.

Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U: Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006, 95 (Suppl 1): S161-S192.CrossRefPubMed

17.

Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T, du Bois A, Kristensen G, Jakobsen A, Sagae S, et al: Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011, 21 (2): 419-423. 10.1097/IGC.0b013e3182070f17.CrossRefPubMed

18.

Le Page C, Ouellet V, Quinn MC, Tonin PN, Provencher DM, Mes-Masson AM: BTF4/BTNA3.2 and GCS as candidate mRNA prognostic markers in epithelial ovarian cancer. Cancer Epidem Biomar. 2008, 17 (4): 913-920. 10.1158/1055-9965.EPI-07-0692.CrossRef

19.

Chatterjee M, Rancso C, Stuhmer T, Eckstein N, Andrulis M, Gerecke C, Lorentz H, Royer HD, Bargou RC: The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma. Blood. 2008, 111 (7): 3714-3722. 10.1182/blood-2007-05-089151.CrossRefPubMed

20.

Otsuka Y, Kedersha NL, Schoenberg DR: Identification of a cytoplasmic complex that adds a cap onto 5′-monophosphate RNA. Mol Cell Biol. 2009, 29 (8): 2155-2167. 10.1128/MCB.01325-08.CrossRefPubMedPubMedCentral

21.

Guay D, Gaudreault I, Massip L, Lebel M: Formation of a nuclear complex containing the p53 tumor suppressor, YB-1, and the Werner syndrome gene product in cells treated with UV light. Int J Biochem Cell Biol. 2006, 38 (8): 1300-1313. 10.1016/j.biocel.2006.01.008.CrossRefPubMed

22.

Vichai V, Kirtikara K: Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc. 2006, 1 (3): 1112-1116. 10.1038/nprot.2006.179.CrossRefPubMed

23.

Kamura T, Yahata H, Amada S, Ogawa S, Sonoda T, Kobayashi H, Mitsumoto M, Kohno K, Kuwano M, Nakano H: Is nuclear expression of Y box-binding protein-1 a new prognostic factor in ovarian serous adenocarcinoma?. Cancer. 1999, 85 (11): 2450-2454. 10.1002/(SICI)1097-0142(19990601)85:11<2450::AID-CNCR21>3.0.CO;2-U.CrossRefPubMed

24.

Huang X, Ushijima K, Komai K, Takemoto Y, Motoshima S, Kamura T, Kohno K: Co-expression of Y box-binding protein-1 and P-glycoprotein as a prognostic marker for survival in epithelial ovarian cancer. Gynecol Oncol. 2004, 93 (2): 287-291. 10.1016/j.ygyno.2004.01.040.CrossRefPubMed

25.

Woolley AG, Algie M, Samuel W, Harfoot R, Wiles A, Hung NA, Tan PH, Hains P, Valova VA, Huschtscha L, et al: Prognostic association of YB-1 expression in breast cancers: a matter of antibody. PLoS One. 2011, 6 (6): e20603-10.1371/journal.pone.0020603.CrossRefPubMedPubMedCentral

26.

Gibb RK, Taylor DD, Wan T, O’Connor DM, Doering DL, Gercel-Taylor C: Apoptosis as a measure of chemosensitivity to cisplatin and taxol therapy in ovarian cancer cell lines. Gynecol Oncol. 1997, 65 (1): 13-22. 10.1006/gyno.1997.4637.CrossRefPubMed

27.

Egawa-Takata T, Endo H, Fujita M, Ueda Y, Miyatake T, Okuyama H, Yoshino K, Kamiura S, Enomoto T, Kimura T, et al: Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer. Cancer Sci. 2010, 101 (10): 2171-2178. 10.1111/j.1349-7006.2010.01670.x.CrossRefPubMed

28.

LaRue KE, Khalil M, Freyer JP: Microenvironmental regulation of proliferation in multicellular spheroids is mediated through differential expression of cyclin-dependent kinase inhibitors. Cancer Res. 2004, 64 (5): 1621-1631. 10.1158/0008-5472.CAN-2902-2.CrossRefPubMed

29.

Xing H, Wang S, Hu K, Tao W, Li J, Gao Q, Yang X, Weng D, Lu Y, Ma D: Effect of the cyclin-dependent kinases inhibitor p27 on resistance of ovarian cancer multicellular spheroids to anticancer chemotherapy. J Cancer Res Clin Oncol. 2005, 131 (8): 511-519. 10.1007/s00432-005-0677-9.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/303/prepub

Title: Low expression of the X-linked ribosomal protein S4 in human serous epithelial ovarian cancer is associated with a poor prognosis
Authors: Serges P Tsofack
Liliane Meunier
Lilia Sanchez
Jason Madore
Diane Provencher
Anne-Marie Mes-Masson
Michel Lebel
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-13-303

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