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The prognostic significance of the increase in the serum M30 and M65 values after chemotherapy and relationship between these values and clinicopathological factors in patients with advanced gastric cancer

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Tumor Biology

Abstract

In some studies, the prognostic and predictive significance of M30 and M65 has been reported to detect response to chemotherapy. In the present study, we aimed at determining the changes of serum M30 and M65 values after chemotherapy and the impact of these values on treatment response and progression-free survival (PFS) and overall survival (OS) of patients with advanced gastric cancer. A total of 31 patients with advanced gastric cancer was included. M30 and M65 values were measured by a quantitative enzyme-linked immunosorbent assay (ELISA) method in serum samples before and 48 h after the first chemotherapy cycle. Pre- and postchemotherapy values of M30 and M65 were compared. The difference between the mean values of serum M30 and M65 before and after chemotherapy was calculated and the prognostic significance of changes for survival was evaluated by univariate and multivariate analysis. Logistic regression analysis was performed to predict response to chemotherapy. Serum M30 and M65 levels were found to be increased significantly after chemotherapy (M30, 582.7 ± 111.5 U/l [pre mean] vs. 983.3 ± 214.1 U/l [post mean], p = 0.01; M65, 2,061.7 ± 431.2 U/l [pre mean] vs. 2,646.3 ± 433.1 U/l [post mean], p = 0.003). Means of the differences of M30 and M65 levels before and 48 h after chemotherapy were 400.5 ± 190 U/l ([M30-difference] M30-D) and 584.6 ± 335.4 U/l (M65-D), respectively. Patients with serum M30-D of <400.5 U/l had better median PFS and OS times than patients with M30-D >400.5 U/l (PFS, 9.9 vs. 4.3 months, p = 0.018 and OS, 13.6 vs. 8.1 months, p = 0.029). In addition, median PFS and OS intervals in patients with serum M65-D > 584.6 U/l were significantly worse than those of patients whose M65-D was lower than or equal to 584.6 U/l (4.1 vs. 11.4 months for PFS, p = 0.002 and 5.7 vs. 13.6 months for OS, p = 0.005). Patients with values above M30-D and M65-D had a better tumor response compared with patients with values below M30-D and M65-D (p = 0.02 and p = 0.006, respectively). In the logistic regression analysis, only M65-D was significantly found to be an independent factor in predicting response to chemotherapy (p = 0.018, OR:1.4). However, only M30 levels after chemotherapy were found to be an independent prognostic factor for PFS in the multivariate analysis. These results showed for the first time that both M30 and M65 in serum samples of patients with advanced gastric cancer were elevated 48 h after chemotherapy and these were poor prognostic factors for both PFS and OS of patients. Moreover, increased serum M65 levels after chemotherapy can be predict tumor response.

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References

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. Roukos DH, Kappas AM. Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol. 2005;2:98–107.

    Article  PubMed  Google Scholar 

  3. Lee KE, Lee HJ, Kim YH, Yu HJ, Yang HK, Kim WH, et al. Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer. Jpn J Clin Oncol. 2003;33:173–9.

    Article  PubMed  Google Scholar 

  4. Lee HK, Lee HS, Yang HK, Kim WH, Lee KU, Choe KJ, et al. Prognostic significance of Bcl-2 and p53 expression in gastric cancer. Int J Colorectal Dis. 2003;18:518–25.

    Article  PubMed  Google Scholar 

  5. Galizia G, Lieto E, Orditura M, Castellano P, Mura AL, Imperatore V, et al. Epidermal growth factor receptor (EGFR) expression is associated with a worse prognosis in gastric cancer patients undergoing curative surgery. World J Surg. 2007;31:1458–68.

    Article  PubMed  Google Scholar 

  6. Caulín C, Salvesen GS, Oshima RG. Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis. J Cell Biol. 1997;138:1379–94.

    Article  PubMed  Google Scholar 

  7. Ueno T, Toi M, Linder S. Detection of epithelial cell death in the body by cytokeratin 18 measurement. Biomed Pharmacother. 2005;59:359–62.

    Article  Google Scholar 

  8. 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;64:1751–6.

    Article  PubMed  CAS  Google Scholar 

  9. 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;10:719–22.

    Article  PubMed  CAS  Google Scholar 

  10. 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;24:669–76.

    Article  PubMed  CAS  Google Scholar 

  11. 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;56:399–404.

    Article  PubMed  Google Scholar 

  12. 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;13:3198–206.

    Article  PubMed  CAS  Google Scholar 

  13. 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;9:645–8.

    Article  PubMed  CAS  Google Scholar 

  14. 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;35:1164–8.

    Article  PubMed  CAS  Google Scholar 

  15. Scott LC, Evans TR, Cassidy J, Harden S, Paul J, Ullah R, et al. Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response. Br J Cancer. 2009;101:410–7.

    Article  PubMed  CAS  Google Scholar 

  16. Hickman JA, Beere HM, Wood AC, Waters CM, Parmar R. Mechanism of cytotoxicity caused by antitumor drugs. Toxicol Lett. 1992;64:553–61.

    Article  PubMed  Google Scholar 

  17. Ulukaya E, Karaagac E, Ari F, Oral AY, Adim SB, Tokullugil AH, et al. Chemotherapy increases caspase-cleaved cytokeratin 18 in the serum of breast cancer patients. Radiol Oncol. 2011;45:116–22.

    Article  PubMed  CAS  Google Scholar 

  18. de Haas EC, di Pietro A, Simpson KL, Meijer C, Suurmeijer A, 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;10:1041–8.

    PubMed  Google Scholar 

  19. Kramer G, Schwarz S, Hägg M, Havelka AM, Linder S. Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006;94:1592–8.

    PubMed  CAS  Google Scholar 

  20. 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;68:309–16.

    Article  PubMed  CAS  Google Scholar 

  21. AJCC (American Joint Committee on Cancer, et al. In: Edge SB, Byrd DR, Compton CC, editors. Cancer Staging Manual. 7th ed. New York: Springer; 2010. p. 117.

    Google Scholar 

  22. James K, Eisenhauer E, Christian M, Terenziani M, Vena D, Muldal A, et al. Measuring response in solid tumors: unidimensional versus bidimensional measurement. J Natl Cancer Inst. 1999;91:523–8.

    Article  PubMed  CAS  Google Scholar 

  23. Renz A, Berdel WE, Kreuter M, Belka C, Schulze-Osthoff K, Los M. Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo. Blood. 2001;98:1542–8.

    Article  PubMed  CAS  Google Scholar 

  24. 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;102:577–82.

    Article  PubMed  CAS  Google Scholar 

  25. Ricci MS, Zong WX. Chemotherapeutic approaches for targeting cell death pathways. Oncologist. 2006;11:342–57.

    Article  PubMed  CAS  Google Scholar 

  26. Blajeski AL, Kottke TJ, Kaufmann SH. A multistep model for paclitaxel-induced apoptosis in human breast cancer cell lines. Exp Cell Res. 2001;270:277–88.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

This study was presented at the ECCO 16-36th ESMO, 2011, European Multidisciplinary Cancer Congress, in a poster session.

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This manuscript was not supported by any financial or other relationships.

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Correspondence to Ahmet Bilici.

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Bilici, A., Ustaalioglu, B.B.O., Ercan, S. et al. The prognostic significance of the increase in the serum M30 and M65 values after chemotherapy and relationship between these values and clinicopathological factors in patients with advanced gastric cancer. Tumor Biol. 33, 2201–2208 (2012). https://doi.org/10.1007/s13277-012-0481-5

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  • DOI: https://doi.org/10.1007/s13277-012-0481-5

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