Vol 90, No 5 (2019)
Research paper
Published online: 2019-04-10

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Prognostic value of tissue plasminogen activator (tPA) in patients with epithelial ovarian cancer undergoing chemotherapy

Justyna Teliga-Czajkowska1, Jacek Sienko2, Katarzyna Jalinik3, Roman Smolarczyk4, Krzysztof Czajkowski2
Pubmed: 30968388
Ginekol Pol 2019;90(5):235-241.

Abstract

Objectives: Tissue plasminogen activator (tPA) is a key enzyme for fibrin degradation and the proteolytic defense against formation of the thrombotic endothelial deposits. tPA is involved in carcinogenesis but its exact role in tumor biology is not very well understood and a prognostic value of tPA remains ambiguous in different cancers. The aim of the study was to assess the prognostic value of plasma tPA in patients with epithelial ovarian cancer (EOC) in the course of the first line chemotherapy. 

Material and methods: the study covered 60 patients with EOC who underwent the 1st line chemotherapy. Plasma tPA was assessed at onset, after 3 and 6 cycles of chemotherapy. The groups were stratified according to tPA level at onset of chemotherapy (low tPA group < 6.5 mg/L, N = 37 and high tPA group > 6.5 mg/L, N = 23). Survival analysis was repeated for the cut-off of tPA level at 6.5 mg/L and 5.1 mg/L after 3 and 6 cycles. 

Results: Only subjects with tPA > 6.5 mg/L at onset of chemotherapy had a significantly lower probability of a 5-year survival (34.8% vs. 72.7%, P < 0.006) and lower chance for disease free survival within 5 years (39.3% vs. 72.7%, P < 0.014). tPA < 6.5 mg/L plasma level evaluated at onset of chemotherapy was an independent marker of better overall survival (RR = 0.44, 95%CI = 0.19–0.98) but not disease-free survival. 

Conclusions: Plasma tPA may serve as a marker of survival if assessed at onset of the first line chemotherapy in patients with ovarian cancer. 

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References

  1. Timp JF, Braekkan SK, Versteeg HH, et al. Epidemiology of cancer-associated venous thrombosis. Blood. 2013; 122(10): 1712–1723.
  2. Rak J, Milsom C, Magnus N, et al. Tissue factor in tumour progression. Best Pract Res Clin Haematol. 2009; 22(1): 71–83.
  3. Rickles FR, Falanga A. Activation of clotting factors in cancer. Cancer Treat Res. 2009; 148: 31–41.
  4. Jaiswal RK, Varshney AK, Yadava PK. Diversity and functional evolution of the plasminogen activator system. Biomed Pharmacother. 2018; 98: 886–898.
  5. Dutta S, Bandyopadhyay C, Bottero V, et al. Angiogenin interacts with the plasminogen activation system at the cell surface of breast cancer cells to regulate plasmin formation and cell migration. Mol Oncol. 2014; 8(3): 483–507.
  6. Sadagopan S, Veettil MV, Chakraborty S, et al. Angiogenin functionally interacts with p53 and regulates p53-mediated apoptosis and cell survival. Oncogene. 2012; 31(46): 4835–4847.
  7. Borgfeldt C, Bendahl PO, Fernö M, et al. High preoperative plasma concentration of tissue plasminogen activator (tPA) is an independent marker for shorter overall survival in patients with ovarian cancer. Gynecol Oncol. 2003; 91(1): 112–117.
  8. Murthi P, Barker G, Nowell CJ, et al. Plasminogen fragmentation and increased production of extracellular matrix-degrading proteinases are associated with serous epithelial ovarian cancer progression. Gynecol Oncol. 2004; 92(1): 80–88.
  9. Hafter R, Klaubert W, Gollwitzer R, et al. Crosslinked fibrin derivatives and fibronectin in ascitic fluid from patients with ovarian cancer compared to ascitic fluid in liver cirrhosis. Thromb Res. 1984; 35(1): 53–64.
  10. Whitley BR, Palmieri D, Twerdi CD, et al. Expression of active plasminogen activator inhibitor-1 reduces cell migration and invasion in breast and gynecological cancer cells. Exp Cell Res. 2004; 296(2): 151–162.
  11. Bell WR. The fibrinolytic system in neoplasia. Semin Thromb Hemost. 1996; 22(6): 459–478.
  12. Ho CH, Yuan CC, Liu SM. Diagnostic and prognostic values of plasma levels of fibrinolytic markers in ovarian cancer. Gynecol Oncol. 1999; 75(3): 397–400.
  13. Chernicky CL, Yi L, Tan H, et al. Tissue-type plasminogen activator is upregulated in metastatic breast cancer cells exposed to insulin-like growth factor-I. Clin Breast Cancer. 2005; 6(4): 340–348.
  14. Paciucci R, Torà M, Díaz VM, et al. The plasminogen activator system in pancreas cancer: role of t-PA in the invasive potential in vitro. Oncogene. 1998; 16(5): 625–633.
  15. Gershtein ES, Kushlinskii NE. Urokinase and tissue plasminogen activators and their inhibitor PAI-1 in human tumors. Bull Exp Biol Med. 2001; 131(1): 67–72.
  16. Sandström M, Johansson M, Sandström J, et al. Expression of the proteolytic factors, tPA and uPA, PAI-1 and VEGF during malignant glioma progression. Int J Dev Neurosci. 1999; 17(5-6): 473–481.
  17. Samulak D, Malinska A, Razik E, et al. A potency of plasminogen activation system in long-term prognosis of endometrial cancer: a pilot study. Eur J Obstet Gynecol Reprod Biol. 2012; 163(2): 193–199.
  18. Andreasen PA, Egelund R, Petersen HH. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci. 2000; 57(1): 25–40.
  19. Menell JS, Cesarman GM, Jacovina AT, et al. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med. 1999; 340(13): 994–1004.
  20. Ridker PM, Vaughan DE, Stampfer MJ, et al. A cross-sectional study of endogenous tissue plasminogen activator, total cholesterol, HDL cholesterol, and apolipoproteins A-I, A-II, and B-100. Arterioscler Thromb. 1993; 13(11): 1587–1592.
  21. Hunt BJ. The effect of BMI on haemostasis: Implications for thrombosis in women's health. Thromb Res. 2017; 151 Suppl 1: S53–S55.
  22. Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood. 2013; 122(20): 3415–3422.
  23. Smith FB, Lee AJ, Hau CM, et al. Tissue-plasminogen activator, plasminogen activator inhibitor and risk of peripheral arterial disease. Atherosclerosis. 1995; 115(1): 35–43.
  24. Morgan ES, Wilson E, Melody T, et al. An observational study of haemostatic changes, leptin and soluble endoglin during pregnancy in women with different BMIs. Blood Coagul Fibrinolysis. 2017; 28(1): 50–55.
  25. Falanga A, Marchetti M, Vignoli A, et al. Clotting mechanisms and cancer: implications in thrombus formation and tumor progression. Clin Adv Hematol Oncol. 2003; 1(11): 673–678.
  26. Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost. 2013; 11(2): 223–233.
  27. Reddel CJ, Tan CW, Chen VM. Thrombin Generation and Cancer: Contributors and Consequences. Cancers (Basel). 2019; 11(1).
  28. 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(2): 276–281.
  29. Whitley BR, Palmieri D, Twerdi CD, et al. Expression of active plasminogen activator inhibitor-1 reduces cell migration and invasion in breast and gynecological cancer cells. Exp Cell Res. 2004; 296(2): 151–162.