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S100A11 is a potential prognostic marker for clear cell renal cell carcinoma

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Abstract

Clear cell renal cell carcinoma (ccRCC) is one of few cancers with rising incidence in North America. The prognosis of ccRCC is variable and difficult to predict. Stratification of patients according to disease aggressiveness can significantly improve patient management. We investigated the expression of the S100A11 protein in 385 patients with primary ccRCC using immunohistochemistry on tissue microarrays. We compared its expression with clinicopathologic parameters and patients’ survival. We also validated our results at the mRNA level on an independent set from The Cancer Genome Atlas. As a dichotomous variable (low vs. high expression), there was a significant association between S100A11 expression and tumor grade, with higher expression associated with higher tumor grades (p < 0.001). High expression was also significantly more frequently seen in higher versus lower stages (56 vs. 28 %). In the univariate analysis, high S100A11 expression was associated with significantly shorter disease-free survival (DFS) (HR = 2.28; p = 0.001). This was maintained in the multivariate analysis (HR = 1.69; p = 0.042). Expression was not associated with overall survival (OS) (p = 0.10). Comparable results were obtained when S100A11 expression was analyzed as a trichotomous variable (low, moderate, or high expression). The Kaplan–Meier survival analyses showed that higher S100A11 expression was associated with statistically significant decrease in DFS (p < 0.001), but not OS (p = 0.1).

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Abbreviations

ccRCC:

Clear cell renal cell carcinoma

DFS:

Disease free survival

OS:

Overall survival

References

  1. Simard EP et al (2012) Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin 62(2):118–128

    Article  PubMed  Google Scholar 

  2. Cheville JC et al (2003) Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol 27(5):612–624

    Article  PubMed  Google Scholar 

  3. Heng DY et al (2013) External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol 14(2):141–148

    Article  PubMed Central  PubMed  Google Scholar 

  4. Faragalla H et al (2012) The clinical utility of miR-21 as a diagnostic and prognostic marker for renal cell carcinoma. J Mol Diagn 14(4):385–392

    Article  PubMed  Google Scholar 

  5. Khella HW et al (2012) Exploring the role of miRNAs in renal cell carcinoma progression and metastasis through bioinformatic and experimental analyses. Tumour Biol 33(1):131–140

    Article  CAS  PubMed  Google Scholar 

  6. Saroufim A et al (2014) Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma. Br J Cancer 110(7):1778–1784

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Tan PH et al (2013) Renal tumors: diagnostic and prognostic biomarkers. Am J Surg Pathol 37(10):1518–1531

    Article  PubMed Central  PubMed  Google Scholar 

  8. Zhang BY et al (2013) Carbonic anhydrase IX (CAIX) is not an independent predictor of outcome in patients with clear cell renal cell carcinoma (ccRCC) after long-term follow-up. BJU Int 111(7):1046–1053

    Article  CAS  PubMed  Google Scholar 

  9. Pasic MD, Samaan S, Yousef GM (2013) Genomic medicine: new frontiers and new challenges. Clin Chem 59(1):158–167

    Article  CAS  PubMed  Google Scholar 

  10. Heizmann CW (2002) The multifunctional S100 protein family. Methods Mol Biol 172:69–80

    CAS  PubMed  Google Scholar 

  11. Marenholz I, Heizmann CW, Fritz G (2004) S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun 322(4):1111–1122

    Article  CAS  PubMed  Google Scholar 

  12. Zimmer DB, Wright Sadosky P, Weber DJ (2003) Molecular mechanisms of S100-target protein interactions. Microsc Res Tech 60(6):552–559

    Article  CAS  PubMed  Google Scholar 

  13. Donato R (1999) Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta 1450(3):191–231

    Article  CAS  PubMed  Google Scholar 

  14. Donato R (2003) Intracellular and extracellular roles of S100 proteins. Microsc Res Tech 60(6):540–551

    Article  CAS  PubMed  Google Scholar 

  15. Nonaka D, Chiriboga L, Rubin BP (2008) Differential expression of S100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors. J Cutan Pathol 35(11):1014–1019

    Article  PubMed  Google Scholar 

  16. Heizmann CW, Fritz G, Schafer BW (2002) S100 proteins: structure, functions and pathology. Front Biosci 7:d1356–d1368

    Article  CAS  PubMed  Google Scholar 

  17. Sakaguchi M et al (2008) S100A11, an dual mediator for growth regulation of human keratinocytes. Mol Biol Cell 19(1):78–85

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. He H et al (2009) S100A11: diverse function and pathology corresponding to different target proteins. Cell Biochem Biophys 55(3):117–126

    Article  CAS  PubMed  Google Scholar 

  19. Delahunt B et al (2014) Advances in renal neoplasia: recommendations from the 2012 International Society of Urological Pathology Consensus Conference. Urology 83(5):969–974

    Article  PubMed  Google Scholar 

  20. Li J et al (2011) S100A expression in normal corneal-limbal epithelial cells and ocular surface squamous cell carcinoma tissue. Mol Vis 17:2263–2271

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Rehman I et al (2004) Dysregulated expression of S100A11 (calgizzarin) in prostate cancer and precursor lesions. Hum Pathol 35(11):1385–1391

    Article  CAS  PubMed  Google Scholar 

  22. Xiao MB et al (2012) High expression of S100A11 in pancreatic adenocarcinoma is an unfavorable prognostic marker. Med Oncol 29(3):1886–1891

    Article  CAS  PubMed  Google Scholar 

  23. Hao J et al (2012) Selective expression of S100A11 in lung cancer and its role in regulating proliferation of adenocarcinomas cells. Mol Cell Biochem 359(1–2):323–332

    Article  CAS  PubMed  Google Scholar 

  24. Meding S et al (2012) Tissue-based proteomics reveals FXYD3, S100A11 and GSTM3 as novel markers for regional lymph node metastasis in colon cancer. J Pathol 228(4):459–470

    Article  CAS  PubMed  Google Scholar 

  25. Melle C et al (2006) Different expression of calgizzarin (S100A11) in normal colonic epithelium, adenoma and colorectal carcinoma. Int J Oncol 28(1):195–200

    CAS  PubMed  Google Scholar 

  26. Liu XG et al (2010) Ca2+-binding protein S100A11: a novel diagnostic marker for breast carcinoma. Oncol Rep 23(5):1301–1308

    CAS  PubMed  Google Scholar 

  27. Torres-Cabala C et al (2006) Proteomic identification of new biomarkers and application in thyroid cytology. Acta Cytol 50(5):518–528

    Article  PubMed  Google Scholar 

  28. Kolin DL et al (2014) Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer. Biol Chem 395(9):1087–1093

    Article  CAS  PubMed  Google Scholar 

  29. Chen H et al (2014) S100 protein family in human cancer. Am J Cancer Res 4(2):89–115

    PubMed Central  PubMed  Google Scholar 

  30. Liu XM et al (2012) Down-regulation of S100A11, a calcium-binding protein, in human endometrium may cause reproductive failure. J Clin Endocrinol Metab 97(10):3672–3683

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Cross SS et al (2005) Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers. Histopathology 46(3):256–269

    Article  CAS  PubMed  Google Scholar 

  32. Jaiswal JK et al (2014) S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells. Nat Commun 5:3795

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Olena Masui and Nicole White-Al Habeeb for their assistance in the study. This work was supported by grants from the Canadian Institute of Health Research (MOP 119606), Kidney Foundation of Canada (KFOC130030), Kidney Cancer Research Network of Canada, and Prostate Cancer Canada Movember Discovery Grants (D2013-39).

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, London Health Sciences Centre, Western University, London, N6G 2V4, Canada

    Manal Gabril

  2. Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, M5B 1T8, Canada

    Hala Girgis, Fabio Rotondo, Samantha Wala, Qiang Ding, Eriny Tawedrous, Maria Pasic, Sahar Al-Haddad & George M. Yousef

  3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A8, Canada

    Hala Girgis, Samantha Wala, Andrew Evans, Sahar Al-Haddad & George M. Yousef

  4. University of Athens, 30 Panepistimiou Street, 106 79, Athens, Greece

    Andreas Scorilas

  5. Division of Medical Oncology and Hematology, Sunnybrook Odette Cancer Center, Toronto, ON, M4N 3M5, Canada

    Georg A. Bjarnason

  6. Department of Laboratory Medicine, St. Joseph’s Health Centre, Toronto, ON, M6R 1B5, Canada

    Maria Pasic

  7. Division of Urologic Oncology, Department of Surgery, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, M5G 2M9, Canada

    Antonio Finelli

  8. Department of Laboratory Medicine, St. Michael’s Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada

    George M. Yousef

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  1. Manal Gabril
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  2. Hala Girgis
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  3. Andreas Scorilas
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  5. Samantha Wala
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  6. Georg A. Bjarnason
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  8. Andrew Evans
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  9. Eriny Tawedrous
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  10. Maria Pasic
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  13. George M. Yousef
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Corresponding author

Correspondence to George M. Yousef.

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Gabril, M., Girgis, H., Scorilas, A. et al. S100A11 is a potential prognostic marker for clear cell renal cell carcinoma. Clin Exp Metastasis 33, 63–71 (2016). https://doi.org/10.1007/s10585-015-9758-6

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  • DOI: https://doi.org/10.1007/s10585-015-9758-6

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