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Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Thrombocytosis and hyperfibrinogenemia are predictive factors of clinical outcomes in high-grade serous ovarian cancer patients

Authors: Zheng Feng, Hao Wen, Rui Bi, Yachen Duan, Wentao Yang, Xiaohua Wu

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Over 20 % of ovarian cancer patients have preoperative thrombocytosis or hyperfibrinogenemia. We aimed to demonstrate the clinical and prognostic significance of thrombocytosis and hyperfibrinogenemia in high-grade serous ovarian cancer (HGSC).

Methods

We retrospectively investigated HGSC patients who underwent primary staging or debulking surgery between April 2005 and June 2013 in our institution. None of these patients had received neoadjuvant chemotherapy. Data, including age, performance status, FIGO stage, serum CA125, platelet count, fibrinogen level, and surgical residual disease, were collected. Thrombocytosis was defined as a platelet count greater than 450 × 109/L, and hyperfibrinogenemia was defined as a fibrinogen level higher than 4.00 g/L. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For the multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which are expressed as hazard ratios (HRs).

Results

A total of 875 consecutive HGSC patients were identified. The median follow-up time was 29 (1–115) months. The median (interquartile range, IQR) preoperative platelet count was 301 (235–383) × 109/L, and 121 (13.8 %) women had thrombocytosis. The median (IQR) preoperative fibrinogen level was 3.85 (3.19–4.45) g/L, and 332 (45.9 %) of the patients had hyperfibrinogenemia. Both preoperative thrombocytosis and hyperfibrinogenemia were associated with an advanced FIGO stage (p = 0.008 and <0.001, respectively), an increased CA125 level (p = 0.004 and 0.001, respectively), more extensive ascites (p < 0.001 and <0.001, respectively), more extensive residual disease (p < 0.001 and <0.001, respectively) and chemosensitivity (p = 0.043 and <0.001, respectively). In the univariate analyses, hyperfibrinogenemia was associated with reduced PFS (p < 0.001) and OS (p < 0.001). However, thrombocytosis was not found to be a potential predictor of PFS (P = 0.098) or OS (p = 0.894). In the multivariate analyses, hyperfibrinogenemia was an independent predictor of OS (p = 0.014) but not PFS (p = 0.062).

Conclusion

Preoperative thrombocytosis and hyperfibrinogenemia reflected tumor burden to some extent and thus influenced treatment outcomes, and the fibrinogen level was found to be useful as a prognostic predictor in the HGSC patients.
Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.PubMedCrossRef Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.PubMedCrossRef
2.
go back to reference Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, et al. Paraneoplastic Thrombocytosis in Ovarian Cancer. N Engl J Med. 2012;366(7):610–8.PubMedPubMedCentralCrossRef Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, et al. Paraneoplastic Thrombocytosis in Ovarian Cancer. N Engl J Med. 2012;366(7):610–8.PubMedPubMedCentralCrossRef
3.
go back to reference Allensworth SK, Langstraat CL, Martin JR, Lemens MA, McGree ME, Weaver AL, et al. Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer. Gynecol Oncol. 2013;130(3):499–504.PubMedPubMedCentralCrossRef Allensworth SK, Langstraat CL, Martin JR, Lemens MA, McGree ME, Weaver AL, et al. Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer. Gynecol Oncol. 2013;130(3):499–504.PubMedPubMedCentralCrossRef
4.
go back to reference Ma X, Wang Y, Sheng H, Tian W, Qi Z, Teng F, et al. Prognostic significance of thrombocytosis, platelet parameters and aggregation rates in epithelial ovarian cancer. J Obstet Gynaecol Res. 2014;40(1):178–83.PubMedCrossRef Ma X, Wang Y, Sheng H, Tian W, Qi Z, Teng F, et al. Prognostic significance of thrombocytosis, platelet parameters and aggregation rates in epithelial ovarian cancer. J Obstet Gynaecol Res. 2014;40(1):178–83.PubMedCrossRef
5.
go back to reference Qiu J, Yu Y, Fu Y, Ye F, Xie X, Lu W. Preoperative plasma fibrinogen, platelet count and prognosis in epithelial ovarian cancer. J Obstet Gynaecol Res. 2012;38(4):651–7.PubMedCrossRef Qiu J, Yu Y, Fu Y, Ye F, Xie X, Lu W. Preoperative plasma fibrinogen, platelet count and prognosis in epithelial ovarian cancer. J Obstet Gynaecol Res. 2012;38(4):651–7.PubMedCrossRef
6.
go back to reference Man YN, Wang YN, Hao J, Liu X, Liu C, Zhu C, et al. Pretreatment Plasma D-Dimer, Fibrinogen, and Platelet Levels Significantly Impact Prognosis in Patients With Epithelial Ovarian Cancer Independently of Venous Thromboembolism. Int J Gynecol Cancer. 2015;25(1):24–32.PubMedCrossRef Man YN, Wang YN, Hao J, Liu X, Liu C, Zhu C, et al. Pretreatment Plasma D-Dimer, Fibrinogen, and Platelet Levels Significantly Impact Prognosis in Patients With Epithelial Ovarian Cancer Independently of Venous Thromboembolism. Int J Gynecol Cancer. 2015;25(1):24–32.PubMedCrossRef
7.
go back to reference Koh SCL, Khalil R, Lim FK, Ilancheran A, Choolani M. The association between fibrinogen, von Willebrand Factor, antithrombin III, and D-dimer levels and survival outcome by 36 months from ovarian cancer. Clin Appl Thromb Hemost. 2006;12(1):3–8.PubMedCrossRef Koh SCL, Khalil R, Lim FK, Ilancheran A, Choolani M. The association between fibrinogen, von Willebrand Factor, antithrombin III, and D-dimer levels and survival outcome by 36 months from ovarian cancer. Clin Appl Thromb Hemost. 2006;12(1):3–8.PubMedCrossRef
8.
go back to reference Tas F, Kilic L, Bilgin E, Keskin S, Sen F, Ciftci R, et al. Clinical and prognostic significance of coagulation assays in advanced epithelial ovarian cancer. Int J Gynecol Cancer. 2013;23(2):276–81.PubMedCrossRef Tas F, Kilic L, Bilgin E, Keskin S, Sen F, Ciftci R, et al. Clinical and prognostic significance of coagulation assays in advanced epithelial ovarian cancer. Int J Gynecol Cancer. 2013;23(2):276–81.PubMedCrossRef
9.
go back to reference Koh SCL, Razvi K, Chan YH, Narasimhan K, Ilancheran A, Low JJ, et al. The association with age, human tissue kallikreins 6 and 10 and hemostatic markers for survival outcome from epithelial ovarian cancer. Arch Gynecol Obstet. 2011;284(1):183–90.PubMedCrossRef Koh SCL, Razvi K, Chan YH, Narasimhan K, Ilancheran A, Low JJ, et al. The association with age, human tissue kallikreins 6 and 10 and hemostatic markers for survival outcome from epithelial ovarian cancer. Arch Gynecol Obstet. 2011;284(1):183–90.PubMedCrossRef
10.
11.
go back to reference Polterauer S, Grimm C, Seebacher V, Concin N, Marth C, Tomovski C, et al. Plasma Fibrinogen Levels and Prognosis in Patients with Ovarian Cancer: A Multicenter Study. Oncologist. 2009;14(10):979–85.PubMedCrossRef Polterauer S, Grimm C, Seebacher V, Concin N, Marth C, Tomovski C, et al. Plasma Fibrinogen Levels and Prognosis in Patients with Ovarian Cancer: A Multicenter Study. Oncologist. 2009;14(10):979–85.PubMedCrossRef
13.
go back to reference Kolodziejczyk J, Ponczek MB. The role of fibrinogen, fibrin and fibrin(ogen) degradation products (FDPs) in tumor progression. Contemp Oncol (Pozn). 2013;17(2):113–9. Kolodziejczyk J, Ponczek MB. The role of fibrinogen, fibrin and fibrin(ogen) degradation products (FDPs) in tumor progression. Contemp Oncol (Pozn). 2013;17(2):113–9.
14.
go back to reference Bode JG, Albrecht U, Haeussinger D, Heinrich PC, Schaper F. Hepatic acute phase proteins - Regulation by IL-6-and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappa B-dependent signaling. Eur J Cell Biol. 2012;91(6–7):496–505.PubMedCrossRef Bode JG, Albrecht U, Haeussinger D, Heinrich PC, Schaper F. Hepatic acute phase proteins - Regulation by IL-6-and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappa B-dependent signaling. Eur J Cell Biol. 2012;91(6–7):496–505.PubMedCrossRef
15.
go back to reference Albrecht U, Yang X, Asselta R, Keitel V, Tenchini ML, Ludwig S, et al. Activation of NF-kappa B by IL-1 beta blocks IL-6-induced sustained STAT3 activation and STAT3-dependent gene expression of the human gamma-fibrinogen gene. Cell Signal. 2007;19(9):1866–78.PubMedCrossRef Albrecht U, Yang X, Asselta R, Keitel V, Tenchini ML, Ludwig S, et al. Activation of NF-kappa B by IL-1 beta blocks IL-6-induced sustained STAT3 activation and STAT3-dependent gene expression of the human gamma-fibrinogen gene. Cell Signal. 2007;19(9):1866–78.PubMedCrossRef
16.
go back to reference Coward J, Kulbe H, Chakravarty P, Leader D, Vassileva V, Leinster DA, et al. Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res. 2011;17(18):6083–96.PubMedPubMedCentralCrossRef Coward J, Kulbe H, Chakravarty P, Leader D, Vassileva V, Leinster DA, et al. Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res. 2011;17(18):6083–96.PubMedPubMedCentralCrossRef
17.
go back to reference Lo CW, Chen MW, Hsiao M, Wang S, Chen CA, Hsiao SM, et al. IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer. Cancer Res. 2011;71(2):424–34.PubMedCrossRef Lo CW, Chen MW, Hsiao M, Wang S, Chen CA, Hsiao SM, et al. IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer. Cancer Res. 2011;71(2):424–34.PubMedCrossRef
18.
go back to reference Egan K, Crowley D, Smyth P, O’Toole S, Spillane C, Martin C, et al. Platelet Adhesion and Degranulation Induce Pro-Survival and Pro-Angiogenic Signalling in Ovarian Cancer Cells. PLoS One. 2011;6(10):e26125.PubMedPubMedCentralCrossRef Egan K, Crowley D, Smyth P, O’Toole S, Spillane C, Martin C, et al. Platelet Adhesion and Degranulation Induce Pro-Survival and Pro-Angiogenic Signalling in Ovarian Cancer Cells. PLoS One. 2011;6(10):e26125.PubMedPubMedCentralCrossRef
19.
go back to reference Labelle M, Begum S, Hynes RO. Direct Signaling between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis. Cancer Cell. 2011;20(5):576–90.PubMedPubMedCentralCrossRef Labelle M, Begum S, Hynes RO. Direct Signaling between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis. Cancer Cell. 2011;20(5):576–90.PubMedPubMedCentralCrossRef
20.
go back to reference Palumbo JS, Potter JM, Kaplan LS, Talmage K, Jackson DG, Degen JL. Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res. 2002;62(23):6966–72.PubMed Palumbo JS, Potter JM, Kaplan LS, Talmage K, Jackson DG, Degen JL. Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res. 2002;62(23):6966–72.PubMed
21.
go back to reference Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11(2):123–34.PubMedCrossRef Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11(2):123–34.PubMedCrossRef
22.
go back to reference Goubran HA, Burnouf T, Radosevic M, El-Ekiaby M. The platelet-cancer loop. Eur J Intern Med. 2013;24(5):393–400.PubMedCrossRef Goubran HA, Burnouf T, Radosevic M, El-Ekiaby M. The platelet-cancer loop. Eur J Intern Med. 2013;24(5):393–400.PubMedCrossRef
Metadata
Title
Thrombocytosis and hyperfibrinogenemia are predictive factors of clinical outcomes in high-grade serous ovarian cancer patients
Authors
Zheng Feng
Hao Wen
Rui Bi
Yachen Duan
Wentao Yang
Xiaohua Wu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2070-2

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