Skip to main content

Advertisement

SpringerLink
Log in

Survivin and HLA-I expression predicts survival of patients with clear cell renal cell carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Altered expression of survivin and leukocyte antigen class I (HLA-I) proteins is associated with tumor progression. This study investigated their expressions in clear cell renal cell carcinoma (ccRCC) tissues for association with a clinical significance of ccRCC patients. Ninety ccRCC and 20 normal tissue samples (i.e., control) were immunohistochemically stained for survivin and HLA-I expression for an association with clinicopathological data and survival of ccRCC patients. Survivin protein was expressed in 82.2 % (74/90) of ccRCC tissue samples compared to 0 % in the normal tissues, and HLA-I protein was expressed in 90 % (18/20) of the normal tissues vs. 67.8 % (61/90) in ccRCC samples. Survivin expression was associated with tumor grade, stage, and lymph node metastasis (p = 0.000, p = 0.016, and p = 0.001, respectively). Conversely, lost HLA-I expression did not have any associations with clinicopathological data (p > 0.05). Survivin-negative patients had a higher tumor-free survival rate than patients with survivin expression (p = 0.037). Patients with normal HLA-I levels had a higher tumor-free survival rate than those with reduced HLA-I levels (p = 0.02). The uni- and multivariate analyses indicated that expression of survivin and HLA-I, individually and in combination, was an independent predictor for survival of ccRCC patients. Overexpression of survivin but reduced HLA-I expression is useful in the prediction of tumor-free survival of ccRCC patients.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008;34:193–205.

    Article  PubMed  Google Scholar 

  2. Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet. 2009;373:1119–32.

    Article  CAS  PubMed  Google Scholar 

  3. Leibovich BC, Lohse CM, Crispen PL, Boorjian SA, Thompson RH, Blute ML, et al. Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma. J Urol. 2010;183:1309–15.

    Article  PubMed  Google Scholar 

  4. Grimm MO, Wolff I, Zastrow S, Fröhner M, Wirth M. Advances in renal cell carcinoma treatment. Ther Adv Urol. 2010;2:11–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Wang GC, Hsieh PS, Hsu HH, Sun GH, Nieh S, Yu CP, et al. Expression of cortactin and survivin in renal cell carcinoma associated with tumor aggressiveness. World J Urol. 2009;27:557–63.

    Article  CAS  PubMed  Google Scholar 

  6. Mita AC, Mita MM, Nawrocki ST, Giles FJ. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin Cancer Res. 2008;14:5000–5.

    Article  CAS  PubMed  Google Scholar 

  7. Parker AS, Leibovich BC, Lohse CM, Sheinin Y, Kuntz SM, Eckel-Passow JE, et al. Development and evaluation of BioScore: a biomarker panel to enhance prognostic algorithms for clear cell renal cell carcinoma. Cancer. 2009;115:2092–103.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Duffy MJ, O’Donovan N, Brennan DJ, Gallagher WM, Ryan BM. Survivin: a promising tumor biomarker. Cancer Lett. 2007;249:49–60.

    Article  CAS  PubMed  Google Scholar 

  9. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–21.

    Article  CAS  PubMed  Google Scholar 

  10. Sharp JD, Hausladen DA, Maher MG, Wheeler MA, Altieri DC, Weiss RM. Bladder cancer detection with urinary survivin, an inhibitor of apoptosis. Front Biosci. 2002;7:e36–41.

    Article  CAS  PubMed  Google Scholar 

  11. Branca M, Giorgi C, Santini D, Di Bonito L, Ciotti M, Costa S, et al. Survivin as a marker of cervical intraepithelial neoplasia and high-risk human papillomavirus and a predictor of virus clearance and prognosis in cervical cancer. Am J Clin Pathol. 2005;124:113–21.

    Article  CAS  PubMed  Google Scholar 

  12. Xiaoyuan C, Longbang C, Jinghua W, Xiaoxiang G, Huaicheng G, Qun Z, et al. Survivin: a potential prognostic marker and chemoradiotherapeutic target for colorectal cancer. Ir J Med Sci. 2010;179:327–35.

    Article  CAS  PubMed  Google Scholar 

  13. Yamashita S, Chujo M, Miyawaki M, Tokuishi K, Anami K, Yamamoto S, et al. Combination of p53AIP1 and survivin expression is a powerful prognostic marker in non-small cell lung cancer. J Exp Clin Cancer Res. 2009;28:22.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Yamamoto H, Ngan CY, Monden M. Cancer cells survive with survivin. Cancer Sci. 2008;99:1709–14.

    Article  CAS  PubMed  Google Scholar 

  15. Zamparese R, Pannone G, Santoro A, Lo Muzio L, Corsi F, Pedicillo MC, et al. Survivin expression in renal cell carcinoma. Cancer Investig. 2008;26:929–35.

    Article  CAS  Google Scholar 

  16. Castedo M, Perfettini JL, Roumier T, Andreau K, Medema R, Kroemer G. Cell death by mitotic catastrophe: a molecular definition. Oncogene. 2004;23:2825–37.

    Article  CAS  PubMed  Google Scholar 

  17. Parker AS, Lohse CM, Leibovich BC, Cheville JC, Sheinin YM, Kwon ED. Comparison of digital image analysis versus visual assessment to assess survivin expression as an independent predictor of survival for patients with clear cell renal cell carcinoma. Hum Pathol. 2008;39:1176–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Garcia-Lora A, Algarra I, Garrido F. MHC class I antigens, immune surveillance, and tumor immune escape. J Cell Physiol. 2003;195:346–55.

    Article  CAS  PubMed  Google Scholar 

  19. Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N, et al. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 2003;9:320–9.

    Article  PubMed  Google Scholar 

  20. Su X, Guo S, Zhou C, Wang D, Ma W, Zhang S. A simple and effective method for cancer immunotherapy by inactivated allogeneic leukocytes infusion. Int J Cancer. 2009;124:1142–51.

    Article  CAS  PubMed  Google Scholar 

  21. Parker AS, Kosari F, Lohse CM, Houston Thompson R, Kwon ED, Murphy L, et al. High expression levels of survivin protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma. Cancer. 2006;107:37–45.

    Article  CAS  PubMed  Google Scholar 

  22. Yuan J, Liu S, Yu Q, Lin Y, Bi Y, Wang Y, et al. Down-regulation of human leukocyte antigen class I (HLA-I) is associated with poor prognosis in patients with clear cell renal cell carcinoma. Acta Histochem. 2013;115:470–4.

    Article  CAS  PubMed  Google Scholar 

  23. Kitamura H, Honma I, Torigoe T, Asanuma H, Sato N, Tsukamoto T. Down-regulation of HLA class I antigen is an independent prognostic factor for clear cell renal cell carcinoma. J Urol. 2007;177:1269–72. discussion 72.

    Article  CAS  PubMed  Google Scholar 

  24. Lu J, Tan M, Huang WC, Li P, Guo H, Tseng LM, et al. Mitotic deregulation by survivin in ErbB2-overexpressing breast cancer cells contributes to Taxol resistance. Clin Cancer Res. 2009;15:1326–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Mahalingam D, Medina EC, Esquivel JA 2nd, Espitia CM, Smith S, Oberheu K, et al. Vorinostat enhances the activity of temsirolimus in renal cell carcinoma through suppression of survivin levels. Clin Cancer Res. 2010;16(1):141–53.

  26. Andersen MH, Pedersen LO, Capeller B, Brocker EB, Becker JC. thor Straten P. Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients. Cancer Res. 2001;61:5964–8.

    CAS  PubMed  Google Scholar 

  27. Schmitz M, Diestelkoetter P, Weigle B, Schmachtenberg F, Stevanovic S, Ockert D, et al. Generation of survivin-specific CD8+ T effector cells by dendritic cells pulsed with protein or selected peptides. Cancer Res. 2000;60:4845–9.

    CAS  PubMed  Google Scholar 

  28. Andersson E, Villabona L, Bergfeldt K, Carlson JW, Ferrone S, Kiessling R, et al. Correlation of HLA-A02* genotype and HLA class I antigen down-regulation with the prognosis of epithelial ovarian cancer. Cancer Immunol Immunother. 2012;61:1243–53.

    Article  CAS  PubMed  Google Scholar 

  29. Tanaka K, Tsuchikawa T, Miyamoto M, Maki T, Ichinokawa M, Kubota KC, et al. Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients. Int J Oncol. 2012;40:965–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Ouyang W, Liao W, Luo CT, Yin N, Huse M, Kim MV, et al. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature. 2012;491:554–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Stickel JS, Stickel N, Hennenlotter J, Klingel K, Stenzl A, Rammensee HG, et al. Quantification of HLA class I molecules on renal cell carcinoma using Edman degradation. BMC Urol. 2011;11:1.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Seliger B, Cabrera T, Garrido F, Ferrone S. HLA class I antigen abnormalities and immune escape by malignant cells. Semin Cancer Biol. 2002;12:3–13.

    Article  CAS  PubMed  Google Scholar 

  33. Montagna D, Turin I, Schiavo R, Montini E, Zaffaroni N, Villa R, et al. Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor. Cytotherapy. 2012;14:80–90.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work were supported by Hunan Provincial Innovation Foundation for Postgraduate (NO. 250171380100015) and supported by the Fundamental Research Funds for the Central Universities of Central South University (NO. 2014zzts079).

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Urology, Xiangya Hospital, The Central South University, 87 Xiangya Road, 410008, Changsha, Hunan, China

    Sulai Liu, Lin Qi & Xiongbing Zu

  2. Department of Urology, The Affiliated Tumor Hospital of Xiangya Medical School, The Central South University, Changsha, China

    Weiqing Han, Shusuan Jiang, Fuhua Zeng & Yu Xie

  3. Department of Rheumatology, Ningbo Medical Center Li Huili Hospital, Ningbo, China

    Qiuxia Yu

  4. Department of Oncology, Xiangya Hospital, The Central South University, Changsha, China

    Yinghui Song

  5. Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Jinyang Yuan

Authors
  1. Sulai Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiuxia Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yinghui Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weiqing Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiongbing Zu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shusuan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jinyang Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fuhua Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yu Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lin Qi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, S., Qi, L., Yu, Q. et al. Survivin and HLA-I expression predicts survival of patients with clear cell renal cell carcinoma. Tumor Biol. 35, 8281–8288 (2014). https://doi.org/10.1007/s13277-014-2058-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2058-y

Keywords

Search

Navigation