Skip to main content

Advertisement

Log in

Comparison of mRNA, Protein, and Urinary Nucleic Acid Levels of S100A8 and S100A9 between Prostate Cancer and BPH

  • Urologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Infections and inflammation in the prostate play a critical role in carcinogenesis, and S100A8 and S100A9 are key mediators in acute and chronic inflammation. Therefore, we investigated the differences of S100A8/A9 expression between prostate cancer (CaP) and benign prostatic hyperplasia (BPH) tissues, and we evaluated the possibilities of urinary nucleic acids of S100A8/A9 as diagnostic and prognostic markers.

Methods

Tissues from 132 CaP patients who underwent prostatectomy or transurethral resection and 90 BPH patients who underwent transurethral prostatectomy were assessed.sd In addition, S100A8 and S100A9 nucleic acid levels were measured in the urine of 283 CaP patients and 363 BPH controls.

Results

S100A8 and S100A9 mRNA levels were lower in CaP than BPH tissues (P < 0.001). S100A8 and S100A9 expression was increased in cancer tissues with poorer prognosis. In 69 specimens from prostatectomy patients, S100A8/A9 were the independent predictor of biochemical recurrence (hazard ratio 5.22, 95 % confidence interval 1.800–15.155, P = 0.002). Immunohistochemical staining revealed that BPH tissues stained more strongly for both S100A8 and S100A9 than CaP tissues (P < 0.001). S100A8 and S100A9 urinary nucleic acid levels were lower in CaP than in BPH (P = 0.001 and <0.001, respectively).

Conclusions

S100A8/A9 levels are lower in CaP than in BPH. Both were more highly expressed in patients with aggressive disease and shorter biochemical recurrence-free time. S100A8/A9 urinary cell-free nucleic acid levels correlated positively with expression levels obtained from tissue staining. Therefore, S100A8/A9 measurement in tissues and urine may have diagnostic and prognostic value in CaP.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. Jung KW, Won YJ, Park S, et al. Cancer statistics in Korea: incidence, mortality and survival in 2005. J Korean Med Sci. 2009;24:995–1003.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Kim D, Choi D, Lim JH, et al. Changes in prostate cancer aggressiveness over a 12-year period in Korea. Korean J Urol. 2012;53:680–5.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37:417–29.

    Article  CAS  PubMed  Google Scholar 

  5. Donato R. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol. 2001;33:637–68.

    Article  CAS  PubMed  Google Scholar 

  6. Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS. Calcium-dependent and -independent interactions of the S100 protein family. Biochem J. 2006;396:201–14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Ehrchen JM, Sunderkotter C, Foell D, Vogl T, Roth J. The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J Leukoc Biol. 2009;86:557–66.

    Article  CAS  PubMed  Google Scholar 

  8. Nemeth J, Stein I, Haag D, et al. S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis. Hepatology. 2009;50:1251–62.

    Article  CAS  PubMed  Google Scholar 

  9. Grebhardt S, Muller-Decker K, Bestvater F, Hershfinkel M, Mayer D. Impact of S100A8/A9 expression on prostate cancer progression in vitro and in vivo. J Cell Physiol. 2014;229:661–1.

    Article  Google Scholar 

  10. Hermani A, Hess J, De Servi B, et al. Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer. Clin Cancer Res. 2005;11:5146–52.

    Article  CAS  PubMed  Google Scholar 

  11. Grebhardt S, Veltkamp C, Strobel P, Mayer D. Hypoxia and HIF-1 increase S100A8 and S100A9 expression in prostate cancer. Int J Cancer. 2012;131:2785–94.

    Article  CAS  PubMed  Google Scholar 

  12. Tidehag V, Hammarsten P, Egevad L, et al. High density of S100A9 positive inflammatory cells in prostate cancer stroma is associated with poor outcome. Eur J Cancer. 2014;50:1829–1835.

    Article  CAS  PubMed  Google Scholar 

  13. Gahan PB, Swaminathan R. Circulating nucleic acids in plasma and serum. Recent developments. Ann N Y Acad Sci. 2008;1137:1–6.

    Article  CAS  PubMed  Google Scholar 

  14. Casadio V, Calistri D, Salvi S, et al. Urine cell-free DNA integrity as a marker for early prostate cancer diagnosis: a pilot study. Biomed Res Int. 2013;2013:270457.

    Article  PubMed Central  PubMed  Google Scholar 

  15. De Maio G, Rengucci C, Zoli W, Calistri D. Circulating and stool nucleic acid analysis for colorectal cancer diagnosis. World J Gastroenterol. 2014;20:957–67.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Casadio V, Calistri D, Tebaldi M, et al. Urine cell-free DNA integrity as a marker for early bladder cancer diagnosis: preliminary data. Urol Oncol. 2013;31:1744–50.

    Article  CAS  PubMed  Google Scholar 

  17. Jahr S, Hentze H, Englisch S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61:1659–65.

    CAS  PubMed  Google Scholar 

  18. Kanduc D, Mittelman A, Serpico R, et al. Cell death: apoptosis versus necrosis (review). Int J Oncol. 2002;21:165–70.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The specimens for this study were provided by the Chungbuk National University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health, Welfare and Family Affairs. All samples were obtained with informed consent under institutional review board–approved protocols (approval GR2010-12-010). This article was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A4A01008753 and 2008-0062611), and by a Grant from the Next Generation BioGreen 21 Program (PJ0081952011), Rural Development Administration, Republic of Korea.

Disclosure

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wun-Jae Kim MD, PhD.

Additional information

Seok Joong Yun and Chunri Yan contributed equally to this article, and both should be considered first author.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 26 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yun, S.J., Yan, C., Jeong, P. et al. Comparison of mRNA, Protein, and Urinary Nucleic Acid Levels of S100A8 and S100A9 between Prostate Cancer and BPH. Ann Surg Oncol 22, 2439–2445 (2015). https://doi.org/10.1245/s10434-014-4194-4

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-014-4194-4

Keywords

Navigation