Top

Published in:

01-04-2020 | Cytostatic Therapy | Original Article

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

Authors: U. Krafft, S. Tschirdewahn, J. Hess, N. N. Harke, B. A. Hadaschik, P. Nyirády, A. Szendröi, M. Szücs, O. Módos, C. Olah, E. Székely, H. Reis, Tibor Szarvas

Published in: Pathology & Oncology Research | Issue 2/2020

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.

Available only for authorised users

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 49:1374–1403PubMed

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 71:96–108CrossRefPubMed

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

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

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 66:42–54CrossRefPubMed

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):1727–1740CrossRefPubMed

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 72:142–150CrossRefPubMed

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 31:1709–1715CrossRefPubMed

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 194:1575–1581CrossRefPubMed

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 13:4407–4414CrossRefPubMed

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 32:1078–1087CrossRefPubMed

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 CrossRefPubMed

13.

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

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 113:429–436CrossRefPubMed

15.

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

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 117:701–710CrossRefPubMed

17.

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

18.

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

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):3307–3316CrossRefPubMedPubMedCentral

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):1873–1884CrossRefPubMedPubMedCentral

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):13147–13152CrossRefPubMedPubMedCentral

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 493:365–372CrossRefPubMed

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. 37:3514–3527CrossRefPubMed

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 10:404–415CrossRefPubMed

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 49:585–595PubMed

Title: STIP1 Tissue Expression Is Associated with Survival in Chemotherapy-Treated Bladder Cancer Patients
Authors: U. Krafft
S. Tschirdewahn
J. Hess
N. N. Harke
B. A. Hadaschik
P. Nyirády
A. Szendröi
M. Szücs
O. Módos
C. Olah
E. Székely
H. Reis
Tibor Szarvas
Publication date: 01-04-2020
Publisher: Springer Netherlands
Keyword: Cytostatic Therapy
Published in: Pathology & Oncology Research / Issue 2/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-019-00689-y

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

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2020

Overexpression of Pyruvate Kinase M2 in Tumor Tissues Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma

Lactate Dehydrogenase-to-Lymphocyte Ratio Represents a Powerful Prognostic Tool of Metastatic Renal Cell Carcinoma Patients Treated with Tyrosine Kinase Inhibitors

Identifying Potential Prognostic Markers for Muscle-Invasive Bladder Urothelial Carcinoma by Weighted Gene Co-Expression Network Analysis

Preliminary Study on Selected Markers of Oxidative Stress, Inflammation and Angiogenesis in Patients with Bladder Cancer

Total Serum Cholesterol and Pancreatic Cancer Risk: What Is the Link?

Effect of COPD on Inflammation, Lymphoid Functions and Progression-Free Survival during First-Line Chemotherapy in Advanced Non-small Cell Lung Cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer