Here, we found that patients with higher preoperative plasma fibrinogen or higher D-Dimer levels had significantly poorer prognosis, suggesting that preoperative plasma fibrinogen and D-Dimer levels may serve as independent prognostic factors for EC patients. Furthermore, combination of fibrinogen and D-Dimer significantly improved the prognosis prediction efficacy for RFS of EC patients.
It has been demonstrated that the coagulation/fibrinolytic systems are implicated in tumorigenesis, progression, and metastasis 9. Abnormal activation of the coagulation/fibrinolytic system has been frequently identified in various cancers 2, 30. Therefore, the degradation products of coagulation/fibrinolytic system have been used as biomarker of tumor load and prognosis 18, 26. Recent researches demonstrated that fibrinogen and D-dimer are both dysregulated and implicated in cancer progress in many different types of cancers 7, 18, 26. The prognostic values of D-dimer and fibrinogen have been investigated in various cancer types 17, 20, 23. Previous studies reported that plasma D-dimer levels were markedly elevated and may predict the prognosis in patients with lung 1, 16, prostate 25 and colorectal carcinoma 3, 15. These data collectively suggest that D-dimer concentration may be a potential biomarker for risk assessment and prognostication of cancer. Recently, a research reported that lower D-dimer levels was significantly associated with longer OS and RFS of EC patients treated with intensity-modulated radiation therapy 34. Higher D-dimer level was also identified as an independent prognosticator in surgically treated EC patients 16. In this study, we also assessed the associations of preoperative plasma D-dimer concentration with OS and RFS of EC patients. Consistent with previous findings 16, 34, our results demonstrated that higher preoperative plasma D-dimer levels were significantly associated with poorer prognosis of EC patients (Table 4). In addition, Kaplan-Meier curve analysis indicated that EC patients with higher preoperative plasma D-dimer levels had a significantly shorter OS and RFS (Fig. 1(C, D)).
Fibrinogen is identified as a major component of tumor stroma and has been demonstrated to be involved in proliferation, invasion, and metastasis of tumor by promoting tumor angiogenesis and supporting the sustained adhesion of tumor cells 22, 29. Previous researches have demonstrated that the disruption of micro vessel resulted to accumulation of fibrinogen, which resulted in the activation of macrophages and monocytes and promoting the secretion of many cytokines and chemokines 13, 14. Higher preoperative plasma fibrinogen level is an independent marker for impaired prognosis of colorectal cancer patients after curative resection 31, esophageal carcinoma 20 and penile cancer 21. Previous reports showed that plasma fibrinogen level may be a useful biomarker in predicting outcomes of EC patients 12. In this study, we found that higher plasma fibrinogen was significantly associated with poorer OS and RFS in EC patients (Table 4). Kaplan-Meier curve analysis demonstrated that EC patients with higher plasma fibrinogen levels had a significantly poorer OS and RFS (Fig. 1(A, B)).
In the stratified analyses, we found that higher preoperative plasma fibrinogen and D-dimer levels were significantly associated with poor prognosis in patients with older age, without lymph node metastasis, with depth of myometrial invasion and in post-menopausal status. These results indicated that the plasma fibrinogen and D-dimer concentration may be modulated by host characteristics through unknown mechanisms. However, the molecular mechanisms modulated plasma fibrinogen and D-dimer concentrations in cancer patients are still unclear. The detailed mechanisms should be investigated in the future.
To further identify the combined effects of plasma D-dimer and fibrinogen levels on EC patient’s prognosis, we grouped the patients according to the levels of the two parameters. Interestingly, our results showed that patients with higher D-dimer levels and higher fibrinogen levels had a significantly worse RFS than patients with any one abnormal parameter. The results indicated that elevated plasma fibrinogen and D-dimer levels contributed to the poor RFS of EC patients synergistically. Previous researches have demonstrated that elevated fibrinogen and D-dimer levels are correlated to the tumor hypercoagulability. Abnormal activations of the coagulation/fibrinolytic system, especially plasma dimerized plasmin fragment D (D-dimer) and fibrinogen, have been frequently identified in cancer patients 2, 30. In this study, our results have suggested that combination of fibrinogen and D-Dimer significantly improved the prognosis prediction efficacy for RFS of EC patients.
In conclusion, our findings suggested that preoperative plasma fibrinogen and D-Dimer concentration may serve as useful biomarkers for prognosis stratification of EC patients. In addition, combination of fibrinogen and D-Dimer significantly improved the prognosis prediction efficacy for RFS of EC patients. Therefore, plasma fibrinogen/D-Dimer may serve as a potential biomarker to predict EC prognosis.