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Published in: Tumor Biology 6/2012

01-12-2012 | Research Article

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

Authors: Ahmet Bilici, Bala Basak Oven Ustaalioglu, Serif Ercan, Mesut Seker, Burcak Erkol Yilmaz, Asuman Orcun, Mahmut Gumus

Published in: Tumor Biology | Issue 6/2012

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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.
Literature
2.
go back to reference Roukos DH, Kappas AM. Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol. 2005;2:98–107.PubMedCrossRef Roukos DH, Kappas AM. Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol. 2005;2:98–107.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference Ueno T, Toi M, Linder S. Detection of epithelial cell death in the body by cytokeratin 18 measurement. Biomed Pharmacother. 2005;59:359–62.CrossRef Ueno T, Toi M, Linder S. Detection of epithelial cell death in the body by cytokeratin 18 measurement. Biomed Pharmacother. 2005;59:359–62.CrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference Hickman JA, Beere HM, Wood AC, Waters CM, Parmar R. Mechanism of cytotoxicity caused by antitumor drugs. Toxicol Lett. 1992;64:553–61.PubMedCrossRef Hickman JA, Beere HM, Wood AC, Waters CM, Parmar R. Mechanism of cytotoxicity caused by antitumor drugs. Toxicol Lett. 1992;64:553–61.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference 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 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
19.
go back to reference 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 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
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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. 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.
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
25.
go back to reference Ricci MS, Zong WX. Chemotherapeutic approaches for targeting cell death pathways. Oncologist. 2006;11:342–57.PubMedCrossRef Ricci MS, Zong WX. Chemotherapeutic approaches for targeting cell death pathways. Oncologist. 2006;11:342–57.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
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
Authors
Ahmet Bilici
Bala Basak Oven Ustaalioglu
Serif Ercan
Mesut Seker
Burcak Erkol Yilmaz
Asuman Orcun
Mahmut Gumus
Publication date
01-12-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0481-5

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