Advertisement

Annals of Surgical Oncology

, Volume 22, Issue 7, pp 2439–2445 | Cite as

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

  • Seok Joong Yun
  • Chunri Yan
  • Pildu Jeong
  • Ho Won Kang
  • Ye-Hwan Kim
  • Eun-Ah Kim
  • Ok-Jun Lee
  • Won Tae Kim
  • Sung-Kwon Moon
  • Isaac Yi Kim
  • Yung-Hyun Choi
  • Wun-Jae Kim
Urologic Oncology

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.

Keywords

Benign Prostatic Hyperplasia Radical Prostatectomy Biochemical Recurrence S100A9 Expression Benign Prostatic Hyperplasia Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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.

Supplementary material

10434_2014_4194_MOESM1_ESM.docx (27 kb)
Supplementary material 1 (DOCX 26 kb)

References

  1. 1.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37:417–29.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 13.
    Gahan PB, Swaminathan R. Circulating nucleic acids in plasma and serum. Recent developments. Ann N Y Acad Sci. 2008;1137:1–6.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 18.
    Kanduc D, Mittelman A, Serpico R, et al. Cell death: apoptosis versus necrosis (review). Int J Oncol. 2002;21:165–70.PubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Seok Joong Yun
    • 1
  • Chunri Yan
    • 1
  • Pildu Jeong
    • 1
  • Ho Won Kang
    • 1
  • Ye-Hwan Kim
    • 1
  • Eun-Ah Kim
    • 1
  • Ok-Jun Lee
    • 2
  • Won Tae Kim
    • 1
  • Sung-Kwon Moon
    • 3
  • Isaac Yi Kim
    • 4
  • Yung-Hyun Choi
    • 5
  • Wun-Jae Kim
    • 1
  1. 1.Department of UrologyChungbuk National University College of MedicineCheongjuRepublic of Korea
  2. 2.Department of PathologyCollege of Medicine, Chungbuk National UniversityCheongjuRepublic of Korea
  3. 3.School of Food Science and TechnologyChung-Ang UniversityAnseongRepublic of Korea
  4. 4.Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer CenterThe Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical SchoolNew BrunswickUSA
  5. 5.Department of BiochemistryDongeui University College of Oriental MedicineBusanRepublic of Korea

Personalised recommendations