A high serum level of M65 is associated with tumour aggressiveness and an unfavourable prognosis for epithelial ovarian cancer
- 280 Downloads
This study was conducted to determine the clinical significance of serum M30 and M65 in epithelial ovarian cancer (EOC).
A total of 56 patients with EOC and 56 healthy women were included in the study. All of the patients received platinum-based chemotherapy. Pretreatment levels of M30 and M65 were measured using the quantitative ELISA method.
The median M30 and M65 serum levels were significantly elevated in the EOC patients compared with the healthy controls (96.7 vs. 69.5, p = 0.028 and 436.4 versus 166.3, p < 0.001, respectively). The cut-off value of 423.4 U/L for M65 determined with ROC analysis, predicted progression with 75.1 % sensitivity and 65.6 % specificity (AUC = 0.708, p = 0.008). Patients with higher M65 levels had shorter progression-free survival (PFS) (p = 0.021). Both M30 and M65 serum levels were significantly higher for serous-type histology (p = 0.001 and p < 0.001, respectively). Increased M65 serum levels were associated with advanced disease (p = 0.005) and higher grade (p = 0.005). Moreover, M65 levels were higher for chemotherapy-resistant patients (p = 0.04). Multivariate analysis revealed that an elevated serum M65 level was the only significant independent prognostic factor (p = 0.039, HR 3.792).
These results indicated that serum M30 and M65 levels were significantly elevated in patients with EOC compared with healthy women. Particularly, high serum M65 levels were associated with poor prognosis and resistance to platinum-based chemotherapy.
KeywordsSerum M65 Biomarker Epithelial ovarian cancer Apoptosis Prognostic
We thank all of our patients and their families for their participation in this study, as well as the investigators and staff from the participating sites. No financial support was received for this work.
Conflict of interest
- 8.Demiray M, Ulukaya EE, Arslan M, Gokgoz S, Saraydaroglu O, Ercan I, Evrensel T, Manavoglu O (2006) 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 24(7):669–676. doi: 10.1080/07357900600981307 PubMedCrossRefGoogle Scholar
- 10.Olofsson MH, Ueno T, Pan Y, Xu R, Cai F, van der Kuip H, Muerdter TE, Sonnenberg M, Aulitzky WE, Schwarz S, Andersson E, Shoshan MC, Havelka AM, Toi M, Linder S (2007) Cytokeratin-18 is a useful serum biomarker for early determination of response of breast carcinomas to chemotherapy. Clin Cancer Res 13(11):3198–3206. doi: 10.1158/1078-0432.CCR-07-0009 PubMedCrossRefGoogle Scholar
- 11.Ausch C, Buxhofer-Ausch V, Olszewski U, Hinterberger W, Ogris E, Schiessel R, Hamilton G (2009) Caspase-cleaved cytokeratin 18 fragment (M30) as marker of postoperative residual tumor load in colon cancer patients. Eur J Surg Oncol 35(11):1164–1168. doi: 10.1016/j.ejso.2009.02.007 PubMedCrossRefGoogle Scholar
- 12.Oyama K, Fushida S, Kinoshita J, Okamoto K, Makino I, Nakamura K, Hayashi H, Inokuchi M, Nakagawara H, Tajima H, Fujita H, Takamura H, Ninomiya I, Kitagawa H, Fujimura T, Ohta T (2012) Serum cytokeratin 18 as a biomarker for gastric cancer. Clin Exp Med. doi: 10.1007/s10238-012-0202-9
- 13.Bilici A, Ustaalioglu BB, Ercan S, Orcun A, Seker M, Salepci T, Gumus M (2011) Is there any impact of plasma M30 and M65 levels on progression-free survival of patients with advanced gastric cancer? Cancer Chemother Pharmacol 68(2):309–316. doi: 10.1007/s00280-010-1480-0 PubMedCrossRefGoogle Scholar
- 18.Behbakht K, Sill MW, Darcy KM, Rubin SC, Mannel RS, Waggoner S, Schilder RJ, Cai KQ, Godwin AK, Alpaugh RK (2011) Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. Gynecol Oncol 123(1):19–26. doi: 10.1016/j.ygyno.2011.06.022 PubMedCrossRefGoogle Scholar
- 19.Cummings J, Ranson M, Lacasse E, Ganganagari JR, St-Jean M, Jayson G, Durkin J, Dive C (2006) Method validation and preliminary qualification of pharmacodynamic biomarkers employed to evaluate the clinical efficacy of an antisense compound (AEG35156) targeted to the X-linked inhibitor of apoptosis protein XIAP. Br J Cancer 95(1):42–48. doi: 10.1038/sj.bjc.6603220 PubMedCrossRefGoogle Scholar
- 20.Karlsen MA, Sandhu N, Hogdall C, Christensen IJ, Nedergaard L, Lundvall L, Engelholm SA, Pedersen AT, Hartwell D, Lydolph M, Laursen IA, Hogdall EV (2012) Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass. Gynecol Oncol 127(2):379–383. doi: 10.1016/j.ygyno.2012.07.106 PubMedCrossRefGoogle Scholar
- 25.Holdenrieder S, Stieber P, VONP J, Raith H, Nagel D, Feldmann K, Seidel D (2006) Early and specific prediction of the therapeutic efficacy in non-small cell lung cancer patients by nucleosomal DNA and cytokeratin-19 fragments. Ann N Y Acad Sci 1075:244–257. doi: 10.1196/annals.1368.033 PubMedCrossRefGoogle Scholar
- 29.de Haas EC, di Pietro A, Simpson KL, Meijer C, Suurmeijer AJ, Lancashire LJ, Cummings J, de Jong S, de Vries EG, Dive C, Gietema JA (2008) Clinical evaluation of M30 and M65 ELISA cell death assays as circulating biomarkers in a drug-sensitive tumor, testicular cancer. Neoplasia 10(10):1041–1048PubMedGoogle Scholar
- 32.Bilici A, Ustaalioglu BB, Ercan S, Seker M, Yilmaz BE, Orcun A, Gumus M (2012) 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. Tumour Biol. doi: 10.1007/s13277-012-0481-5