Skip to main content

Renal Cell Carcinoma Biomarkers in Circulation

  • Chapter
  • First Online:
Book cover Cancer Biomarkers in Body Fluids
  • 1229 Accesses

Abstract

  • Molecular pathology of renal cell carcinoma (RCC)

  • Circulating cell-free nucleic acid content as RCC biomarkers

  • Circulating RCC miRNA biomarkers

  • Circulating cytokine and angiogenic factors as RCC biomarkers

  • Circulating RCC cells

  • Circulating endothelial and hematopoietic lineage cells as RCC biomarkers

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gang F, Guorong L, An Z, Anne GP, Christian G, Jacques T. Prediction of clear cell renal cell carcinoma by integrity of cell-free DNA in serum. Urology. 2010;75(2):262–5. doi:10.1016/j.urology.2009.06.048.

    Article  PubMed  Google Scholar 

  2. Hauser S, Zahalka T, Ellinger J, Fechner G, Heukamp LC. A VONR, et al. Cell-free circulating DNA: Diagnostic value in patients with renal cell cancer. Anticancer Res. 2010;30(7):2785–9.

    CAS  PubMed  Google Scholar 

  3. Feng G, Ye X, Fang F, Pu C, Huang H, Li G. Quantification of plasma cell-free DNA in predicting therapeutic efficacy of sorafenib on metastatic clear cell renal cell carcinoma. Dis Markers. 2013;34(2):105–11. doi:10.3233/DMA-120950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ellinger J, Muller DC, Muller SC, Hauser S, Heukamp LC, von Ruecker A, et al. Circulating mitochondrial DNA in serum: a universal diagnostic biomarker for patients with urological malignancies. Urol Oncol. 2012;30(4):509–15. doi:10.1016/j.urolonc.2010.03.004.

    Article  CAS  PubMed  Google Scholar 

  5. Feng G, Li G, Gentil-Perret A, Tostain J, Genin C. Elevated serum-circulating RNA in patients with conventional renal cell cancer. Anticancer Res. 2008;28(1A):321–6.

    CAS  PubMed  Google Scholar 

  6. Feng G, Jiang F, Pan C, Pu C, Huang H, Li G. Quantification of peripheral blood CD133 mRNA in identifying metastasis and in predicting recurrence of patients with clear cell renal cell carcinoma. Urol Oncol. 2014;32(1):44 e9–14. doi:10.1016/j.urolonc.2013.06.003.

    Article  Google Scholar 

  7. de Martino M, Klatte T, Haitel A, Marberger M. Serum cell-free DNA in renal cell carcinoma: a diagnostic and prognostic marker. Cancer. 2012;118(1):82–90. doi:10.1002/cncr.26254.

    Article  PubMed  Google Scholar 

  8. Hauser S, Zahalka T, Fechner G, Muller SC, Ellinger J. Serum DNA hypermethylation in patients with kidney cancer: results of a prospective study. Anticancer Res. 2013;33(10):4651–6.

    CAS  PubMed  Google Scholar 

  9. von Knobloch R, Hegele A, Brandt H, Varga Z, Wille S, Kalble T, et al. High frequency of serum DNA alterations in renal cell carcinoma detected by fluorescent microsatellite analysis. Int J Cancer. 2002;98(6):889–94.

    Article  Google Scholar 

  10. Perego RA, Corizzato M, Brambilla P, Ferrero S, Bianchi C, Fasoli E, et al. Concentration and microsatellite status of plasma DNA for monitoring patients with renal carcinoma. Eur J Cancer. 2008;44(7):1039–47. doi:10.1016/j.ejca.2008.03.008.

    Article  CAS  PubMed  Google Scholar 

  11. Goessl C, Heicappell R, Munker R, Anker P, Stroun M, Krause H, et al. Microsatellite analysis of plasma DNA from patients with clear cell renal carcinoma. Cancer Res. 1998;58(20):4728–32.

    CAS  PubMed  Google Scholar 

  12. Gonzalgo ML, Eisenberger CF, Lee SM, Trock BJ, Marshall FF, Hortopan S, et al. Prognostic significance of preoperative molecular serum analysis in renal cancer. Clin Cancer Res. 2002;8(6):1878–81.

    CAS  PubMed  Google Scholar 

  13. Wulfken LM, Moritz R, Ohlmann C, Holdenrieder S, Jung V, Becker F, et al. MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One. 2011;6(9):e25787. doi:10.1371/journal.pone.0025787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Redova M, Poprach A, Nekvindova J, Iliev R, Radova L, Lakomy R, et al. Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. J Transl Med. 2012;10:55. doi:10.1186/1479-5876-10-55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhao A, Li G, Peoc’h M, Genin C, Gigante M. Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol. 2013;94(1):115–20. doi:10.1016/j.yexmp.2012.10.005.

    Article  CAS  PubMed  Google Scholar 

  16. Iwamoto H, Kanda Y, Sejima T, Osaki M, Okada F, Takenaka A. Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma. Int J Oncol. 2014;44(1):53–8. doi:10.3892/ijo.2013.2169.

    CAS  PubMed  Google Scholar 

  17. Wang C, Hu J, Lu M, Gu H, Zhou X, Chen X, et al. A panel of five serum miRNAs as a potential diagnostic tool for early-stage renal cell carcinoma. Sci Rep. 2015;5:7610. doi:10.1038/srep07610.

    Article  CAS  PubMed  Google Scholar 

  18. Teixeira AL, Ferreira M, Silva J, Gomes M, Dias F, Santos JI, et al. Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumour Biol. 2014;35(5):4057–66. doi:10.1007/s13277-013-1531-3.

    Article  CAS  PubMed  Google Scholar 

  19. Bussolati B, Bruno S, Grange C, Ferrando U, Camussi G. Identification of a tumor-initiating stem cell population in human renal carcinomas. FASEB J. 2008;22(10):3696–705. doi:10.1096/fj.08-102590.

    Article  CAS  PubMed  Google Scholar 

  20. Su Kim D, Choi YD, Moon M, Kang S, Lim JB, Kim KM, et al. Composite three-marker assay for early detection of kidney cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(3):390–8. doi:10.1158/1055-9965.EPI-12-1156.

    Article  PubMed  Google Scholar 

  21. Pena C, Lathia C, Shan M, Escudier B, Bukowski RM. Biomarkers predicting outcome in patients with advanced renal cell carcinoma: Results from sorafenib phase III Treatment Approaches in Renal Cancer Global Evaluation Trial. Clin Cancer Res. 2010;16(19):4853–63. doi:10.1158/1078-0432.CCR-09-3343.

    Article  CAS  PubMed  Google Scholar 

  22. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, et al. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009;27(20):3312–8. doi:10.1200/JCO.2008.19.5511.

    Article  CAS  PubMed  Google Scholar 

  23. Escudier B, Cosaert J, Pisa P. Bevacizumab: direct anti-VEGF therapy in renal cell carcinoma. Expert Rev Anticancer Ther. 2008;8(10):1545–57. doi:10.1586/14737140.8.10.1545.

    Article  CAS  PubMed  Google Scholar 

  24. Negrier S, Perol D, Menetrier-Caux C, Escudier B, Pallardy M, Ravaud A, et al. Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6--from the Groupe Francais d’Immunotherapie. J Clin Oncol. 2004;22(12):2371–8. doi:10.1200/JCO.2004.06.121.

    Article  CAS  PubMed  Google Scholar 

  25. Ramankulov A, Lein M, Kristiansen G, Loening SA, Jung K. Plasma osteopontin in comparison with bone markers as indicator of bone metastasis and survival outcome in patients with prostate cancer. Prostate. 2007;67(3):330–40. doi:10.1002/pros.20540.

    Article  PubMed  Google Scholar 

  26. Tran HT, Liu Y, Zurita AJ, Lin Y, Baker-Neblett KL, Martin AM, et al. Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of phase 2 and phase 3 trials. Lancet Oncol. 2012;13(8):827–37. doi:10.1016/S1470-2045(12)70241-3.

    Article  CAS  PubMed  Google Scholar 

  27. Zurita AJ, Jonasch E, Wang X, Khajavi M, Yan S, Du DZ, et al. A cytokine and angiogenic factor (CAF) analysis in plasma for selection of sorafenib therapy in patients with metastatic renal cell carcinoma. Ann Oncol. 2012;23(1):46–52. doi:10.1093/annonc/mdr047.

    Article  CAS  PubMed  Google Scholar 

  28. Motzer RJ, Hutson TE, Hudes GR, Figlin RA, Martini JF, English PA, et al. Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma. Cancer Chemother Pharmacol. 2014;74(4):739–50. doi:10.1007/s00280-014-2539-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Armstrong AJ, George DJ, Halabi S. Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin. J Clin Oncol. 2012;30(27):3402–7. doi:10.1200/JCO.2011.40.9631.

    Article  CAS  PubMed  Google Scholar 

  30. Won Y, Song HJ, Kang TW, Kim JJ, Han BD, Lee SW. Pattern analysis of serum proteome distinguishes renal cell carcinoma from other urologic diseases and healthy persons. Proteomics. 2003;3(12):2310–6. doi:10.1002/pmic.200300590.

    Article  CAS  PubMed  Google Scholar 

  31. Engwegen JY, Mehra N, Haanen JB, Bonfrer JM, Schellens JH, Voest EE, et al. Validation of SELDI-TOF MS serum protein profiles for renal cell carcinoma in new populations. Lab Invest. 2007;87(2):161–72. doi:10.1038/labinvest.3700503.

    Article  CAS  PubMed  Google Scholar 

  32. Hara T, Honda K, Ono M, Naito K, Hirohashi S, Yamada T. Identification of 2 serum biomarkers of renal cell carcinoma by surface enhanced laser desorption/ionization mass spectrometry. J Urol. 2005;174(4 Pt 1):1213–7.

    Article  CAS  PubMed  Google Scholar 

  33. Liu JS, Li HZ, Zhang YS, Wang P, Yan WG, Xie J, et al. Screening for the serum differential proteins of renal cell carcinoma using magnetic beads-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2011;33(3):287–91. doi:10.3881/j.issn.1000-503X.2011.03.016.

    CAS  PubMed  Google Scholar 

  34. Chinello C, Gianazza E, Zoppis I, Mainini V, Galbusera C, Picozzi S, et al. Serum biomarkers of renal cell carcinoma assessed using a protein profiling approach based on ClinProt technique. Urology. 2010;75(4):842–7. doi:10.1016/j.urology.2009.09.050.

    Article  PubMed  Google Scholar 

  35. Engwegen JY, Mehra N, Haanen JB, Schellens JH, Voest EE, Beijnen JH. Identification of two new serum protein profiles for renal cell carcinoma. Oncol Rep. 2009;22(2):401–8.

    CAS  PubMed  Google Scholar 

  36. Wood SL, Rogers M, Cairns DA, Paul A, Thompson D, Vasudev NS, et al. Association of serum amyloid A protein and peptide fragments with prognosis in renal cancer. Br J Cancer. 2010;103(1):101–11. doi:10.1038/sj.bjc.6605720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Xu G, Xiang CQ, Lu Y, Kang XN, Wang WJ, Liao P, et al. Proteomic analysis in combination with CT diagnosis to distinguish renal cell carcinoma from renal benign masses. Zhonghua Yi Xue Za Zhi. 2008;88(12):858–60.

    PubMed  Google Scholar 

  38. Xu G, Xiang CQ, Lu Y, Wang WJ, Kang XN, Liao P, et al. SELDI-TOF-MS-based serum proteomic screening in combination with CT scan distinguishes renal cell carcinoma from benign renal tumors and healthy persons. Technol Cancer Res Treat. 2009;8(3):225–30.

    Article  CAS  PubMed  Google Scholar 

  39. Xu G, Xiang CQ, Lu Y, Kang XN, Liao P, Ding Q, et al. Application of SELDI-TOF-MS to identify serum biomarkers for renal cell carcinoma. Cancer Lett. 2009;282(2):205–13. doi:10.1016/j.canlet.2009.03.017.

    Article  CAS  PubMed  Google Scholar 

  40. Gianazza E, Chinello C, Mainini V, Cazzaniga M, Squeo V, Albo G, et al. Alterations of the serum peptidome in renal cell carcinoma discriminating benign and malignant kidney tumors. J Proteomics. 2012;76 Spec No.:125–40. doi: 10.1016/j.jprot.2012.07.032.

  41. Yang J, Yang J, Gao Y, Zhao L, Liu L, Qin Y, et al. Identification of potential serum proteomic biomarkers for clear cell renal cell carcinoma. PLoS One. 2014;9(11):e111364. doi:10.1371/journal.pone.0111364.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Bluemke K, Bilkenroth U, Meye A, Fuessel S, Lautenschlaeger C, Goebel S, et al. Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma correlates with prognosis. Cancer Epidemiol Biomarkers Prev. 2009;18(8):2190–4. doi:10.1158/1055-9965.EPI-08-1178.

    Article  CAS  PubMed  Google Scholar 

  43. Gradilone A, Iacovelli R, Cortesi E, Raimondi C, Gianni W, Nicolazzo C, et al. Circulating tumor cells and “suspicious objects” evaluated through CellSearch(R) in metastatic renal cell carcinoma. Anticancer Res. 2011;31(12):4219–21.

    CAS  PubMed  Google Scholar 

  44. Mancuso P, Burlini A, Pruneri G, Goldhirsch A, Martinelli G, Bertolini F. Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood. 2001;97(11):3658–61.

    Article  CAS  PubMed  Google Scholar 

  45. Beerepoot LV, Mehra N, Vermaat JS, Zonnenberg BA, Gebbink MF, Voest EE. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol. 2004;15(1):139–45.

    Article  CAS  PubMed  Google Scholar 

  46. Shaked Y, Henke E, Roodhart JM, Mancuso P, Langenberg MH, Colleoni M, et al. Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents. Cancer Cell. 2008;14(3):263–73. doi:10.1016/j.ccr.2008.08.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Shaked Y, Ciarrocchi A, Franco M, Lee CR, Man S, Cheung AM, et al. Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science. 2006;313(5794):1785–7. doi:10.1126/science.1127592.

    Article  CAS  PubMed  Google Scholar 

  48. Bhatt RS, Zurita AJ, O’Neill A, Norden-Zfoni A, Zhang L, Wu HK, et al. Increased mobilisation of circulating endothelial progenitors in von Hippel-Lindau disease and renal cell carcinoma. Br J Cancer. 2011;105(1):112–7. doi:10.1038/bjc.2011.186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Farace F, Gross-Goupil M, Tournay E, Taylor M, Vimond N, Jacques N, et al. Levels of circulating CD45(dim)CD34(+)VEGFR2(+) progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors. Br J Cancer. 2011;104(7):1144–50. doi:10.1038/bjc.2011.72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gruenwald V, Beutel G, Schuch-Jantsch S, Reuter C, Ivanyi P, Ganser A, et al. Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib. BMC Cancer. 2010;10:695. doi:10.1186/1471-2407-10-695.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Mancuso A, Di Paola ED, Leone A, Catalano A, Calabro F, Cerbone L, et al. Phase II escalation study of sorafenib in patients with metastatic renal cell carcinoma who have been previously treated with anti-angiogenic treatment. BJU Int. 2012;109(2):200–6. doi:10.1111/j.1464-410X.2011.10421.x.

    Article  CAS  PubMed  Google Scholar 

  52. Vroling L, van der Veldt AA, de Haas RR, Haanen JB, Schuurhuis GJ, Kuik DJ, et al. Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib. Angiogenesis. 2009;12(1):69–79. doi:10.1007/s10456-009-9133-9.

    Article  CAS  PubMed  Google Scholar 

  53. Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, et al. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009;69(4):1553–1560. doi: 10.1158/0008-5472.CAN-08-1921.

  54. Ko JS, Rayman P, Ireland J, Swaidani S, Li G, Bunting KD, et al. Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res. 2010;70(9):3526–3536. doi: 10.1158/0008-5472.CAN-09-3278.

  55. Ozao-Choy J, Ma G, Kao J, Wang GX, Meseck M, Sung M, et al. The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res. 2009;69(6):2514–2522. doi: 10.1158/0008-5472.CAN-08-4709.

  56. van Cruijsen H, van der Veldt AA, Vroling L, Oosterhoff D, Broxterman HJ, Scheper RJ, et al. Sunitinib-induced myeloid lineage redistribution in renal cell cancer patients: CD1c+ dendritic cell frequency predicts progression-free survival. Clin Cancer Res. 2008;14(18):5884–92. doi:10.1158/1078-0432.CCR-08-0656.

    Article  PubMed  Google Scholar 

  57. Adotevi O, Pere H, Ravel P, Haicheur N, Badoual C, Merillon N, et al. A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients. J Immunother. 2010;33(9):991–8. doi:10.1097/CJI.0b013e3181f4c208.

    Article  CAS  PubMed  Google Scholar 

  58. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794–9. doi:10.1200/JCO.2008.21.4809.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Dakubo, G.D. (2017). Renal Cell Carcinoma Biomarkers in Circulation. In: Cancer Biomarkers in Body Fluids. Springer, Cham. https://doi.org/10.1007/978-3-319-48360-3_10

Download citation

Publish with us

Policies and ethics