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Diagnostic value of serum M30 and M65 in patients with nasopharyngeal carcinoma

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Tumor Biology

Abstract

M30 and M65 are circulating fragments of cytokeratin 18 released during apoptotic cell death and regarded as markers of cell death in patients with various tumor types. Our aim was to investigate the clinical and prognostic significance of the serum M30 and M65 concentrations in patients with advanced nasopharyngeal carcinoma. Thirty-two patients with nasopharyngeal cancer and 32 control subjects were investigated. Serum samples were obtained on first admission before any treatment was initiated. Serum M30 and M65 concentrations were measured by quantitative enzyme-linked immunosorbent assay. Median serum M30 (181.5 vs. 45.5 U/L, p < 0.001) and M65 (384.2 vs. 179.1 U/L, p < 0.001) concentrations were significantly higher in patients with advanced nasopharyngeal carcinomas than in controls. receiver operating characteristic (ROC) analysis showed that a cutoff for M30 of 225 U/L had a sensitivity of 62.5 % and a specificity of 73.9 % (area under the curve (AUC) = 0.592, 95 % confidence interval (CI) 35.3–83.2, p = 0.44), while a cutoff for M65 of 423.4 U/L had a sensitivity of 75.1 % and a specificity of 65.6 % (AUC = 0.562, 95 % CI 36.0–76.5, p = 0.60). However, serum M30 and M65 were not important prognostic factors for progression-free survival. There were no statistically significant correlations between serum M30 and M65 concentrations and clinicodemographical variables. Serum M30 and M65 concentrations were found to have a diagnostic value in nasopharyngeal cancer. However, neither M30 nor M65 serum levels played a prognostic role in the outcome in nasopharyngeal cancer patients.

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References

  1. Li ZQ, Xia YF, Liu Q, Yi W, Liu XF, Han F, et al. Radiotherapy-related typing in 842 patients in Canton with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006;66(4):1011–6. doi:10.1016/j.ijrobp.2006.06.028.

    Article  PubMed  Google Scholar 

  2. Leung TW, Tung SY, Sze WK, Wong FC, Yuen KK, Lui CM, et al. Treatment results of 1070 patients with nasopharyngeal carcinoma: an analysis of survival and failure patterns. Head Neck. 2005;27(7):555–65. doi:10.1002/hed.20189.

    Article  PubMed  Google Scholar 

  3. Zhang L, Zhao C, Ghimire B, Hong MH, Liu Q, Zhang Y, et al. The role of concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma among endemic population: a meta-analysis of the phase III randomized trials. BMC Cancer. 2010;10:558. doi:10.1186/1471-2407-10-558.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lee AW, Poon YF, Foo W, Law SC, Cheung FK, Chan DK, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure. Int J Radiat Oncol Biol Phys. 1992;23(2):261–70.

    Article  CAS  PubMed  Google Scholar 

  5. Lv X, Xiang YQ, Cao SM, Qian CN, Li NW, Guo L, et al. Prospective validation of the prognostic value of elevated serum vascular endothelial growth factor in patients with nasopharyngeal carcinoma: more distant metastases and shorter overall survival after treatment. Head Neck. 2011;33(6):780–5. doi:10.1002/hed.21541.

    Article  PubMed  Google Scholar 

  6. Chang KP, Hao SP, Chang JH, Wu CC, Tsang NM, Lee YS, et al. Macrophage inflammatory protein-3alpha is a novel serum marker for nasopharyngeal carcinoma detection and prediction of treatment outcomes. Clin Cancer Res. 2008;14(21):6979–87. doi:10.1158/1078-0432.CCR-08-0090.

    Article  CAS  PubMed  Google Scholar 

  7. Ku NO, Liao J, Omary MB. Apoptosis generates stable fragments of human type I keratins. J Biol Chem. 1997;272(52):33197–203.

    Article  CAS  PubMed  Google Scholar 

  8. Ueno T, Toi M, Linder S. Detection of epithelial cell death in the body by cytokeratin 18 measurement. Biomed Pharmacother. 2005;59 Suppl 2:S359–62.

    Article  CAS  PubMed  Google Scholar 

  9. Kramer G, Erdal H, Mertens HJ, Nap M, Mauermann J, Steiner G, et al. Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18. Cancer Res. 2004;64(5):1751–6.

    Article  CAS  PubMed  Google Scholar 

  10. Galluzzi L, Maiuri MC, Vitale I, Zischka H, Castedo M, Zitvogel L, et al. Cell death modalities: classification and pathophysiological implications. Cell Death Differ. 2007;14(7):1237–43. doi:10.1038/sj.cdd.4402148.

    Article  CAS  PubMed  Google Scholar 

  11. Cummings J, Ranson M, Butt F, Moore D, Dive C. Qualification of M30 and M65 ELISAs as surrogate biomarkers of cell death: long term antigen stability in cancer patient plasma. Cancer Chemother Pharmacol. 2007;60(6):921–4. doi:10.1007/s00280-007-0437-4.

    Article  CAS  PubMed  Google Scholar 

  12. Demiray M, Ulukaya EE, Arslan M, Gokgoz S, Saraydaroglu O, Ercan I, et al. Response to neoadjuvant chemotherapy in breast cancer could be predictable by measuring a novel serum apoptosis product, caspase-cleaved cytokeratin 18: a prospective pilot study. Cancer Invest. 2006;24(7):669–76. doi:10.1080/07357900600981307.

    Article  CAS  PubMed  Google Scholar 

  13. Ulukaya E, Yilmaztepe A, Akgoz S, Linder S, Karadag M. The levels of caspase-cleaved cytokeratin 18 are elevated in serum from patients with lung cancer and helpful to predict the survival. Lung Cancer. 2007;56(3):399–404. doi:10.1016/j.lungcan.2007.01.015.

    Article  PubMed  Google Scholar 

  14. Olofsson MH, Ueno T, Pan Y, Xu R, Cai F, van der Kuip H, et al. Cytokeratin-18 is a useful serum biomarker for early determination of response of breast carcinomas to chemotherapy. Clin Cancer Res. 2007;13(11):3198–206. doi:10.1158/1078-0432.CCR-07-0009.

    Article  CAS  PubMed  Google Scholar 

  15. Ausch C, Buxhofer-Ausch V, Olszewski U, Hinterberger W, Ogris E, Schiessel R, et al. Caspase-cleaved cytokeratin 18 fragment (M30) as marker of postoperative residual tumor load in colon cancer patients. Eur J Surg Oncol. 2009;35(11):1164–8. doi:10.1016/j.ejso.2009.02.007.

    Article  CAS  PubMed  Google Scholar 

  16. Oyama K, Fushida S, Kinoshita J, Okamoto K, Makino I, Nakamura K, et al. Serum cytokeratin 18 as a biomarker for gastric cancer. Clin Exp Med. 2012. doi:10.1007/s10238-012-0202-9.

    PubMed  Google Scholar 

  17. Bilici A, Ustaalioglu BB, Ercan S, Orcun A, Seker M, Salepci T, et al. Is there any impact of plasma M30 and M65 levels on progression-free survival of patients with advanced gastric cancer? Cancer Chemother Pharmacol. 2011;68(2):309–16. doi:10.1007/s00280-010-1480-0.

    Article  CAS  PubMed  Google Scholar 

  18. Yaman E, Coskun U, Sancak B, Buyukberber S, Ozturk B, Benekli M. Serum M30 levels are associated with survival in advanced gastric carcinoma patients. Int Immunopharmacol. 2010;10(7):719–22. doi:10.1016/j.intimp.2010.03.013.

    Article  CAS  PubMed  Google Scholar 

  19. Ozturk B, Coskun U, Sancak B, Yaman E, Buyukberber S, Benekli M. Elevated serum levels of M30 and M65 in patients with locally advanced head and neck tumors. Int Immunopharmacol. 2009;9(5):645–8. doi:10.1016/j.intimp.2009.02.004.

    Article  CAS  PubMed  Google Scholar 

  20. SB BD, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual 7th ed ed. New York, NY: Springer; 2010

  21. Wu YX, Wang JH, Wang H, Yang XY. Study on expression of Ki-67, early apoptotic protein M30 in endometrial carcinoma and their correlation with prognosis. Zhonghua bing li xue za zhi Chin J Pathol. 2003;32(4):314–8.

    Google Scholar 

  22. de Haas EC, di Pietro A, Simpson KL, Meijer C, Suurmeijer AJ, Lancashire LJ, et al. Clinical evaluation of M30 and M65 ELISA cell death assays as circulating biomarkers in a drug-sensitive tumor, testicular cancer. Neoplasia. 2008;10(10):1041–8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kramer G, Schwarz S, Hagg M, Havelka AM, Linder S. Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006;94(11):1592–8. doi:10.1038/sj.bjc.6603129.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Koelink PJ, Lamers CB, Hommes DW, Verspaget HW. Circulating cell death products predict clinical outcome of colorectal cancer patients. BMC Cancer. 2009;9:88. doi:10.1186/1471-2407-9-88.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Schutte B, Henfling M, Kolgen W, Bouman M, Meex S, Leers MP, et al. Keratin 8/18 breakdown and reorganization during apoptosis. Exp Cell Res. 2004;297(1):11–26. doi:10.1016/j.yexcr.2004.02.019.

    Article  CAS  PubMed  Google Scholar 

  26. Li XM, Huang WG, Yi H, Cheng AL, Xiao ZQ. Proteomic analysis to identify cytokeratin 18 as a novel biomarker of nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 2009;135(12):1763–75. doi:10.1007/s00432-009-0623-3.

    Article  CAS  PubMed  Google Scholar 

  27. Ueno T, Toi M, Biven K, Bando H, Ogawa T, Linder S. Measurement of an apoptotic product in the sera of breast cancer patients. Eur J Cancer. 2003;39(6):769–74.

    Article  CAS  PubMed  Google Scholar 

  28. Greystoke A, Dean E, Saunders MP, Cummings J, Hughes A, Ranson M, et al. Multi-level evidence that circulating CK18 is a biomarker of tumour burden in colorectal cancer. Br J Cancer. 2012;107(9):1518–24. doi:10.1038/bjc.2012.416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dive C, Smith RA, Garner E, Ward T, George-Smith SS, Campbell F, et al. Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer. Br J Cancer. 2010;102(3):577–82. doi:10.1038/sj.bjc.6605494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Oven Ustaalioglu B, Bilici A, Ercan S, Orcun A, Seker M, Ozkan A, et al. Serum M30 and M65 values in patients with advanced stage non-small-cell lung cancer compared with controls. Clin Transl Oncol. 2012;14(5):356–61.

    Article  CAS  PubMed  Google Scholar 

  31. Brandt D, Volkmann X, Anstatt M, Langer F, Manns MP, Schulze-Osthoff K, et al. Serum biomarkers of cell death for monitoring therapy response of gastrointestinal carcinomas. Eur J Cancer. 2010;46(8):1464–73. doi:10.1016/j.ejca.2010.01.037.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Institute of Oncology, Istanbul University, Capa, 34390, Istanbul, Turkey

    Fatma Sen, Ibrahim Yildiz, Hatice Odabas, Leyla Kilic, Meltem Ekenel, Sevil Bavbek & Mert Basaran

  2. Department of Radiation Oncology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey

    Makbule Tambas, Ahmet Karadeniz & Musa Altun

  3. Department of Basic Oncology, Institute of Oncology, Istanbul University, Capa, 34390, Istanbul, Turkey

    Murat Serilmez & Derya Duranyildiz

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  1. Fatma Sen
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  2. Ibrahim Yildiz
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Correspondence to Makbule Tambas.

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Sen, F., Yildiz, I., Odabas, H. et al. Diagnostic value of serum M30 and M65 in patients with nasopharyngeal carcinoma. Tumor Biol. 36, 1039–1044 (2015). https://doi.org/10.1007/s13277-014-2708-0

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  • DOI: https://doi.org/10.1007/s13277-014-2708-0

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