Tumor Biology

, Volume 36, Issue 11, pp 8903–8911 | Cite as

Preoperative D-dimers as an independent prognostic marker in cervical carcinoma

  • Yao-Ling Luo
  • Pei-Dong Chi
  • Xin Zheng
  • Lin Zhang
  • Xue-Ping Wang
  • Hao Chen
Research Article

Abstract

Activation of coagulation and fibrinolysis has been observed in many tumors. Our study aimed to investigate the clinical and prognostic significance of various plasma coagulation tests in patients with cervical cancer. A total of 296 patients with cervical cancer were included in the analysis. Patients were followed up for at least 60 months until death. Pretreatment parameters including activated partial thromboplastin time, D-dimer, fibrinogen, prothrombin time, thrombin time, lactate dehydrogenase, and squamous cell carcinoma antigen were evaluated. Prothrombin time (hazard ratio = 1.825; P = 0.006) and plasma D-dimer levels (hazard ratio = 2.179; P = 0.036) were identified as significant independent predictors of overall survival. Patients with elevated D-dimer levels had a significantly shorter overall survival compared with those with low-D-dimer levels (<0.5 μg/ml) in the stage I subgroup (n = 98, P = 0.019) and stage II subgroup (n = 77, P = 0.044). D-dimer levels differed significantly according to mortality (P < 0.001), stage I versus stage II (P = 0.030), and stage I versus stage III/IV (P = 0.038). DD level of patients with chemotherapy and/or radiotherapy was higher than patients with other treatment (P < 0.001). Patients with a low-D-dimer level (<0.5 μg/ml) showed a significantly better 5-year overall survival (OS) compared with patients with an increased D-dimer level for different histological typing of squamous cell carcinoma (SCC) (P = 0.001) and non-SCC (P < 0.043). In conclusion, the pretreatment plasma D-dimer level is a potential prognostic factor for cervical cancer.

Keywords

Cervical cancer Coagulation Prothrombin time D-dimer Prognosis 

Notes

Acknowledgments

We thank the Director of Clinical Laboratories, Sun Yat-sen University Cancer Center, Guangzhou, China, Prof. Wan-Li Liu, for providing support on research conditions in this study and making substantial contributions to its conception and design.

Conflicts of interest

None

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Benedet JL, Odicino F, Maisonneuve P, et al. Carcinoma of the cervix uteri. J Epidemiol Biostat. 2001;6:7–43.PubMedGoogle Scholar
  3. 3.
    Chen J, Macdonald OK, Gaffney DK. Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix. Obstet Gynecol. 2008;111(6):1394–402.CrossRefPubMedGoogle Scholar
  4. 4.
    Vinh-Hung V, Bourgain C, Vlastos G, et al. Prognostic value of histopathology and trends in cervical cancer: a SEER population study. BMC Cancer. 2007;7:164.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Intaraphet S, Kasatpibal N, Siriaunkgul S, et al. Prognostic impact of histology in patients with cervical squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma. Asian Pac J Cancer Prev. 2013;14(9):5355–60.CrossRefPubMedGoogle Scholar
  6. 6.
    Gadducci A, Tana R, Cosio S, Genazzani AR. The serum assay of tumor markers in the prognostic evaluation, treatment monitoring and follow-up of patients with cervical cancer: a review of the literature. Crit Rev Oncol Hematol. 2008;66:10–20.CrossRefPubMedGoogle Scholar
  7. 7.
    Reesink-Peters N, van der Velden J, Ten Hoor KA, Boezen HM, de Vries EG, Schilthuis MS, et al. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer. J Clin Oncol. 2005;23:1455–62.CrossRefPubMedGoogle Scholar
  8. 8.
    Lyman GH, Khorana AA. Cancer, clots and consensus: new understanding of an old problem. J Clin Oncol. 2009;27:4821–6.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kessler CM. The link between cancer and venous thromboembolism: a review. Am J Clin Oncol. 2009;32:S3–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Falanga A, Marchetti M, Vignoli A, Balducci D. Clotting mechanisms and cancer: implications in thrombus formation and tumor progression. Clin Adv Hematol Oncol. 2003;1:673–8.PubMedGoogle Scholar
  11. 11.
    Khorana AA. Risk assessment and prophylaxis for VTE in cancer patients. J Natl Compr Canc Netw. 2011;9:789–97.CrossRefPubMedGoogle Scholar
  12. 12.
    Langer F, Holstein K, Eifrig B, Bokemeyer C. Haemostatic aspects in clinical oncology. Hamostaseologie. 2008;28:472–80.PubMedGoogle Scholar
  13. 13.
    Zhang Y, Deng Y, Luther T, et al. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest. 1994;94:1320–7.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bromberg ME, Sundaram R, Homer RJ, Garen A, Konigsberg WH. Role of tissue factor in metastasis: functions of the cytoplasmic and extracellular domains of the molecule. Thromb Haemost. 1999;82:88–92.PubMedGoogle Scholar
  15. 15.
    Jiang X, Bailly MA, Panetti TS, Cappello M, Konigsberg WH, Bromberg ME. Formation of tissue factor-factor VIIa-factor Xa complex promotes cellular signaling and migration of human breast cancer cells. J Thromb Haemost. 2004;2:93–101.CrossRefPubMedGoogle Scholar
  16. 16.
    Kasthuri RS, Taubman MB, Mackman N. Role of tissue factor in cancer. J Clin Oncol. 2009;27:4834–8.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ruf W, Disse J, Carneiro-Lobo TC, Yokota N, Schaffner F. Tissue factor and cell signalling in cancer progression and thrombosis. J Thromb Haemost. 2011;9 Suppl 1:306–15.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Rak J, Milsom C, Magnus N, Yu J. Tissue factor in tumour progression. Best Pract Res Clin Haematol. 2009;22:71–83.CrossRefPubMedGoogle Scholar
  19. 19.
    Strauss HG, Laban C, Lautenschläger C, Buchmann J, Schneider I, Koelbl H, et al. SCC antigen in the serum as an independent prognostic factor in operable squamous cell carcinoma of the cervix. Eur J Cancer. 2002;38(15):1987–91.CrossRefPubMedGoogle Scholar
  20. 20.
    Naschitz JE, Yeshurun D, Lev LM. Thromboembolism in cancer. Changing trends. Cancer. 1993;71:1384–90.CrossRefPubMedGoogle Scholar
  21. 21.
    Mytnik M, Stasko J. D-dimer, plasminogen activator inhibitor-1, prothrombin fragments and protein C—role in prothrombotic state of colorectal cancer. Neoplasma. 2011;58:235–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Welsh J, Smith JD, Yates KR, et al. Tissue factor expression determines tumour cell coagulation kinetics. Int J Lab Hematol. 2012;34:396–402.CrossRefPubMedGoogle Scholar
  23. 23.
    Tas F, Kilic L, Bilgin E, et al. Clinical and prognostic significance of coagulation assays in advanced epithelial ovarian cancer. Int J Gynecol Cancer. 2013;23:276–81.CrossRefPubMedGoogle Scholar
  24. 24.
    Wen-Hui C, Lin-Quan T, Feng-Wei W, Chang-Peng L, Xiao-Peng T, Xiao-Xia H, et al. Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma. BMC Cancer. 2014;14:583.CrossRefGoogle Scholar
  25. 25.
    Yong-Xin Z, Zhong-Min Y, Jing F, Ying-Jun S, Wei-Li W, Yun-Qing M. High plasma D-dimer level is associated with decreased survival in patients with lung cancer: a meta-analysis. Tumor Biol. 2013;34:3701–4.CrossRefGoogle Scholar
  26. 26.
    Yamamoto M, Yoshinaga K, Matsuyama A, Iwasa T, Osoegawa A, Tsujita E, et al. Plasma D-dimer level as a mortality predictor in patients with advanced or recurrent colorectal cancer. Oncology. 2012;83:10–5.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yao-Ling Luo
    • 1
  • Pei-Dong Chi
    • 1
  • Xin Zheng
    • 1
  • Lin Zhang
    • 1
  • Xue-Ping Wang
    • 1
  • Hao Chen
    • 1
  1. 1.State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouChina

Personalised recommendations