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Prognostic Significance of CD24 in Clear Cell Renal Cell Carcinoma

  • Original Article
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Pathology & Oncology Research

Abstract

The role of cancer stem cells in the initiation and progression of cancer has become a well-studied area of emerging research, and stem cells with different surface markers have been identified in various types of cancer. CD24 is a membrane protein that acts as the ligand for P-selectin and has been defined as a stem cell marker of colonic cancer. The immunohistochemical expression of CD24 is associated with worse patient outcomes in small cell lung cancer, hepatocellular carcinoma, breast cancer, and colon cancer. In this study, we used immunohistochemistry to determine CD24 expression in clear cell, papillary and chromophobe renal cell carcinoma and investigated its relationship with other clinicopathological parameters and prognosis. A total of 108 cases of clear cell, 12 papillary and 13 choromophobe renal cell carcinoma were examined. Clinicopathological features including age, gender, vascular invasion, tumor necrosis, and T stage were recorded. Clinical stage and overall survival and disease-free survival times were recorded. The immunohistochemical expression of CD24 was classified as low or high based on the percentage and intensity of positive staining. CD24 expression was associated with both tumor grade and recurrence rates. The survival analysis revealed that patients with high CD24 expression exhibited significantly lower overall and disease-free survival. Increased expression of CD24 is related to the prognosis of clear cell renal cell carcinoma. This is the first study identifying a strong association between CD24 expression levels and survival. Thus, CD24 expression may aid in predicting prognosis in clear cell renal cell carcinoma.

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References

  1. Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A, Bray F (2015) International variations and trends in renal cell carcinoma incidence and mortality. Eur Urol 67:519–530

    Article  PubMed  Google Scholar 

  2. Sun C, Song H, Zhang H, Hou C, Zhai T, Huang L, Zhang L (2012) CD133 expression in renal cell carcinoma (RCC) is correlated with nuclear hypoxia-inducing factor 1α (HIF-1α). J Cancer Res Clin Oncol 138:1619–1624

    Article  CAS  PubMed  Google Scholar 

  3. Axelson H, Johansson ME (2013) Renal stem cells and their implications for kidney cancer. Semin Cancer Biol 23:56–61

    Article  CAS  PubMed  Google Scholar 

  4. Carrasco E, Alvarez PJ, Prados J, Melguizo C, Rama AR, Aránega A, Rodríguez-Serrano F (2014) Cancer stem cells and their implication in breast cancer. Eur J Clin Investig 44:678–687

    Article  CAS  Google Scholar 

  5. Guler G, Balci S, Costinean S, Ussakli CH, Irkkan C, Suren D, Sari E, Altundag K, Ozisik Y, Jones S, Bacher J, Shapiro CL, Huebner K (2012) Stem cell-related markers in primary breast cancers and associated metastatic lesions. Mod Pathol 25:949–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bane A, Viloria-Petit A, Pinnaduwage D, Mulligan AM, O’Malley FP, Andrulis IL (2013) Clinical-pathologic significance of cancer stem cell marker expression in familial breast cancers. Breast Cancer Res Treat 140:195–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983–3988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    CAS  PubMed  Google Scholar 

  9. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen M, Geng J (2006) P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp 54:75–84

    Article  CAS  Google Scholar 

  11. Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H, Sleeman JP (2005) CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res 65:10783–10793

    Article  CAS  PubMed  Google Scholar 

  12. Suzuki T, Kiyokawa N, Taguchi T, Sekino T, Katagiri YU, Fujimoto J (2001) CD24 induces apoptosis in human B cells via the glycolipid-enriched membrane domains/rafts-mediated signaling system. J Immunol 166:5567–5577

    Article  CAS  PubMed  Google Scholar 

  13. Kristiansen G, Sammar M, Altevogt P (2004) Tumour biological aspects of CD24, a mucin-like adhesion molecule. J Mol Histol 35:255–262

    Article  CAS  PubMed  Google Scholar 

  14. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367:645–648

    Article  CAS  PubMed  Google Scholar 

  15. Yu Z, Pestell TG, Lisanti MP, Pestell RG (2012) Cancer stem cells. Int J Biochem Cell Biol 44:2144–2151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sammar M, Aigner S, Hubbe M, Schirrmacher V, Schachner M, Vestweber D, Altevogt P (1994) Heat-stable antigen (CD24) as ligand for mouse P-selectin. Int Immunol 6:1027–1036

    Article  CAS  PubMed  Google Scholar 

  17. Gracz AD, Fuller MK, Wang F, Li L, Stelzner M, Dunn JC, Martin MG, Magness ST (2013) Brief report: CD24 and CD44 mark human intestinal epithelial cell populations with characteristics of active and facultative stem cells. Stem Cells 31:2024–2030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Deng W, Gu L, Li X, Zheng J, Zhang Y, Duan B, Cui J, Dong J, Du J (2016) CD24 associates with EGFR and supports EGF/EGFR signaling via RhoA in gastric cancer cells. J Transl Med 14:32

    Article  PubMed  Google Scholar 

  19. Kristiansen G, Winzer KJ, Mayordomo E, Bellach J, Schlüns K, Denkert C, Dahl E, Pilarsky C, Altevogt P, Guski H, Dietel M (2003) CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res 9:4906–4913

    CAS  PubMed  Google Scholar 

  20. Bretz NP, Salnikov AV, Perne C, Keller S, Wang X, Mierke CT, Fogel M, Erbe-Hofmann N, Schlange T, Moldenhauer G, Altevogt P (2012) CD24 controls Src/STAT3 activity in human tumors. Cell Mol Life Sci 69:3863–3879

    Article  CAS  PubMed  Google Scholar 

  21. Droz D, Zachar D, Charbit L, Gogusev J, Chrétein Y, Iris L (1990) Expression of the human nephron differentiation molecules in renal cell carcinomas. Am J Pathol 137:895–905

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Lee HJ, Kim DI, Kwak C, Ku JH, Moon KC (2008) Expression of CD24 in clear cell renal cell carcinoma and its prognostic significance. Urol 72:603–607

    Article  PubMed  Google Scholar 

  23. Wu JX, Zhao YY, Wu X, An HX (2014) Clinicopathological and prognostic significance of CD24 overexpression in patients with gastric cancer: a meta-analysis. PLoS One 9:e114746

    Article  PubMed  PubMed Central  Google Scholar 

  24. Senner V, Sturm A, Baur I, Schrell UH, Distel L, Paulus W (1999) CD24 promotes invasion of glioma cells in vivo. J Neuropathol Exp Neurol 58:795–802

    Article  CAS  PubMed  Google Scholar 

  25. Friederichs J, Zeller Y, Hafezi-Moghadam A, Gröne HJ, Ley K, Altevogt P (2000) The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells. Cancer Res 60:6714–6722

    CAS  PubMed  Google Scholar 

  26. Tanaka T, Terai Y, Kogata Y, Ashihara K, Maeda K, Fujiwara S, Yoo S, Tanaka Y, Tsunetoh S, Sasaki H, Kanemura M, Tanabe A, Ohmichi M (2015) CD24 expression as a marker for predicting clinical outcome and invasive activity in uterine cervical cancer. Oncol Rep 34:2282–2288

    CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Deniz Arik.

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Ethical Approval

Our study was approved by the Non-Drug Clinical Research Ethics Board of Medicine Faculty of Eskişehir Osmangazi University (14 March 2013, Order No: 07).

Funding

This study was supported by the Eskişehir Osmangazi University Scientific Research Projects Commission (Project No: 2014–132).

Conflict of Interest

The authors declare no conflict of interest.

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Arik, D., Can, C., Dündar, E. et al. Prognostic Significance of CD24 in Clear Cell Renal Cell Carcinoma. Pathol. Oncol. Res. 23, 409–416 (2017). https://doi.org/10.1007/s12253-016-0128-8

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  • DOI: https://doi.org/10.1007/s12253-016-0128-8

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