Skip to main content

Advertisement

SpringerLink
Log in

STIP1 Tissue Expression Is Associated with Survival in Chemotherapy-Treated Bladder Cancer Patients

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

To optimize treatment decisions in advanced bladder cancer (BC), we aimed to assess the therapy predictive value of STIP1 with regard to cisplatin therapy. Cisplatin-based chemotherapy represents the standard first-line systemic treatment of advanced bladder cancer. Since novel immunooncologic agents are already available for cisplatin-resistant or ineligible patients, biological markers are needed for the prediction of cisplatin resistance. STIP1 expression was analyzed in paraffin-embedded bladder cancer tissue samples of 98 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Furthermore, pre-chemotherapy serum STIP1 concentrations were determined in 48 BC patients by ELISA. Results were correlated with the clinicopathological and follow-up data. Stronger STIP1 nuclear staining was associated with worse OS in both the whole patient group (p = 0.034) and the subgroup of patients who received at least 2 cycles of chemotherapy (p = 0.043). These correlations remained significant also in the multivariable analyses (p = 0.035 and p = 0.040). Stronger STIP1 cytoplasmatic immunostaining correlated with shorter PFS both in the whole cohort (p = 0.045) and in the subgroup of patients who received at least 2 cycles of chemotherapy (p = 0.026). Elevated STIP1 serum levels were associated with older patient’s age, but we found no correlation between STIP1 serum levels and patients’ outcome. Our results suggest that tissue STIP1 analysis might be used for the prediction of cisplatin-resistance in BC. In contrast, pretreatment STIP1 serum levels showed no predictive value for chemotherapy response and survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403

    CAS  PubMed  Google Scholar 

  2. Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F (2017) Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 71:96–108

    Article  PubMed  Google Scholar 

  3. Stein JP, Skinner DG (2006) Radical cystectomy for invasive bladder cancer: long-term results of a standard procedure. World J Urol 24:296–304

    Article  PubMed  Google Scholar 

  4. Stadler WM, Lerner SP (2003) Perioperative chemotherapy in locally advanced bladder cancer. Lancet. 361:1922–1923

    Article  PubMed  Google Scholar 

  5. Leow JJ, Martin-Doyle W, Rajagopal PS, Patel CG, Anderson EM, Rothman AT et al (2014) Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol 66:42–54

    Article  CAS  PubMed  Google Scholar 

  6. Rouanne M, Roumiguié M, Houédé N, Masson-Lecomte A, Colin P, Pignot G et al (2018) Development of immunotherapy in bladder cancer: present and future on targeting PD(L)1 and CTLA-4 pathways. World J Urol 36(11):1727–1740

    Article  CAS  PubMed  Google Scholar 

  7. Seiler R, Oo HZ, Tortora D, Clausen TM, Wang CK, Kumar G et al (2017) An Oncofetal glycosaminoglycan modification provides therapeutic access to cisplatin-resistant bladder Cancer. Eur Urol 72:142–150

    Article  CAS  PubMed  Google Scholar 

  8. Ozcan MF, Dizdar O, Dincer N, Balcı S, Guler G, Gok B et al (2013) Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy. Urol Oncol 31:1709–1715

    Article  CAS  PubMed  Google Scholar 

  9. Hemdan T, Malmström P-UU, Jahnson S, Segersten U (2015) Emmprin expression predicts response and survival following cisplatin containing chemotherapy for bladder Cancer: a validation study. J Urol 194:1575–1581

    Article  CAS  PubMed  Google Scholar 

  10. Als AB, Dyrskjot L, von der Maase H, Koed K, Mansilla F, Toldbod HE et al (2007) Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. Clin Cancer Res 13:4407–4414

    Article  CAS  PubMed  Google Scholar 

  11. van Rhijn BW, Catto JW, Goebell PJ, Knuchel R, Shariat SF, van der Poel HG et al (2014) Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice. Urol Oncol 32:1078–1087

    Article  PubMed  Google Scholar 

  12. Krafft U, Tschirdewahn S, Hess J, Harke NN, Hadaschik B, Olah C, Krege S, Nyirády P, Szendröi A, Szücs M, Módos O, Székely E, Reis H, Szarvas T (2019) Validation of survivin and HMGA2 as biomarkers for cisplatin resistance in bladder cancer. Urol Oncol. https://doi.org/10.1016/j.urolonc.2019.04.015

    Article  PubMed  Google Scholar 

  13. Zhang S, Shao J, Su F (2018) Prognostic significance of STIP1 expression in human cancer: a meta-analysis. Clin Chim Acta 486:168–176

    Article  CAS  PubMed  Google Scholar 

  14. Krege S, Rexer H, vom Dorp F, de Geeter P, Klotz T, Retz M et al (2014) Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05). BJU Int 113:429–436

    Article  CAS  PubMed  Google Scholar 

  15. Nicolet CM, Craig EA (1989) Isolation and characterization of STI1, a stress-inducible gene from Saccharomyces cerevisiae. Mol Cell Biol 9:3638–3646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Longshaw VM, Chapple JP, Balda MS, Cheetham ME, Blatch GL (2004) Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTI1 is regulated by cell cycle kinases. J Cell Sci 117:701–710

    Article  CAS  PubMed  Google Scholar 

  17. Odunuga OO, Longshaw VM, Blatch GL (2004) Hop: more than an Hsp70/Hsp90 adaptor protein. Bioessays. 26:1058–1068

    Article  CAS  PubMed  Google Scholar 

  18. Johnson BD, Schumacher RJ, Ross ED, Toft DO (1998) Hop modulates Hsp70/Hsp90 interactions in protein folding. J Biol Chem 273:3679–3686

    Article  CAS  PubMed  Google Scholar 

  19. Zanata SM, Lopes MH, Mercadante AF et al (2002) Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection. EMBO J 21(13):3307–3316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang TH, Chao A, Tsai CL, Chang CL et al (2010) Stress-induced phosphoprotein 1 as a secreted biomarker for human ovarian cancer promotes cancer cell proliferation. Mol Cell Proteomics 9(9):1873–1884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Roffé M, Beraldo FH, Bester R (2010) Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR. Proc Natl Acad Sci U S A 107(29):13147–13152

    Article  PubMed  PubMed Central  Google Scholar 

  22. Chen Z, Xu L, Su T, Ke Z, Peng Z, Zhang N et al (2017) Autocrine STIP1 signaling promotes tumor growth and is associated with disease outcome in hepatocellular carcinoma. Biochem Biophys Res Commun 493:365–372

    Article  CAS  PubMed  Google Scholar 

  23. Su T, Liao J, Dai Z, Xu L, Chen S, Wang Y et al (2018) Stress-induced phosphoprotein 1 mediates hepatocellular carcinoma metastasis after insufficient radiofrequency ablation. Oncogene. 37:3514–3527

    Article  CAS  PubMed  Google Scholar 

  24. Skalnikova H, Martinkova J, Hrabakova R, Halada P, Dziechciarkova M, Hajduch M et al (2011) Cancer drug-resistance and a look at specific proteins: Rho GDP-dissociation inhibitor 2, Y-box binding protein 1, and HSP70/90 organizing protein in proteomics clinical application. J Proteome Res 10:404–415

    Article  CAS  PubMed  Google Scholar 

  25. Kim S, Cho H, Nam EJ, Kim SW, Kim YT, Park YW et al (2010) Autoantibodies against stress-induced phosphoprotein-1 as a novel biomarker candidate for ovarian cancer. Genes Chromosom Cancer 49:585–595

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by_NKFIH / FK 12443, NVKP 16-1-2016-004 and by the ÙNKP-18-4-SE-66 New National Excellence Program of the Ministry of Human Capacities. Dr. T. Szarvas was supported by a János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

Author information

Author notes

  1. H. Reis and Tibor Szarvas contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany

    U. Krafft, S. Tschirdewahn, J. Hess, N. N. Harke, B. A. Hadaschik & Tibor Szarvas

  2. Department of Urology, Semmelweis University, Budapest, Hungary

    P. Nyirády, A. Szendröi, M. Szücs, O. Módos, C. Olah & Tibor Szarvas

  3. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary

    E. Székely

  4. Institute of Pathology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany

    H. Reis

Authors
  1. U. Krafft
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Tschirdewahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Hess
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. N. Harke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. A. Hadaschik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Nyirády
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Szendröi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Szücs
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. O. Módos
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. Olah
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. E. Székely
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. H. Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tibor Szarvas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tibor Szarvas.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krafft, U., Tschirdewahn, S., Hess, J. et al. STIP1 Tissue Expression Is Associated with Survival in Chemotherapy-Treated Bladder Cancer Patients. Pathol. Oncol. Res. 26, 1243–1249 (2020). https://doi.org/10.1007/s12253-019-00689-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-019-00689-y

Keywords

Search

Navigation