Abstract
BackgroundIncreasing evidence supported an association between cancer and coagulation system. We aimed to identify prognostic values of coagulation biomarkers in epithelial ovarian cancer (EOC).MethodsA retrospective study was conducted on patients who underwent optimal tumor debulking followed by platinum-based chemotherapy at our institution. The predictive value of coagulation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for recurrence-free survival (RFS) and overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis.ResultsWe involved 482 EOC patients and followed up for 64 (range, 36–87) months. According to ROC curves, D-dimer and International normalized ratio (INR) had superior predictive value than other coagulation indexes, with area under curve (AUC) of 0.758 and 0.742. Patients were then stratified into three combined D-dimer and INR (DD-INR) groups based on the cut-off value of 0.97 mg/L and 0.86, respectively. Through regression analysis, we demonstrated that age (HR 1.273; 95%CI 1.048–2.047; p = 0.045), pathological grade (HR 1.419; 95% CI 1.102–2.491; p = 0.032), clinical stage (HR 2.038; 95%CI 1.284–3.768; p = 0.008), CA-125 (HR 1.426; 95%CI 1.103–1.894; p = 0.038) and DD-INR (HR 2.412; 95%CI 1.683–3.241; p = 0.009) were independent prognostic factors. Survival analysis showed that patients with higher DD-INR experienced poor survival (p = 0.0013 for RFS and p = 0.0068 for OS). Further subgroup analysis revealed that evaluated DD-INR was significantly associated with poor survival among patients with advanced stage (p = 0.0028 for RFS and p = 0.0180 for OS).ConclusionOur findings suggested that coagulation indexes, especially the combined DD-INR were promising biomarkers for prognosis stratification in EOC patients, especially those with advanced clinical stages.
Highlights
Increasing evidence supported an association between cancer and coagulation system
According to the Receiver operating characteristic (ROC) curves of coagulation variables, D-dimer and International normalized ratio (INR) had superior predictive value for epithelial ovarian cancer (EOC) survival compared to activated partial thromboplastin time (APTT), Prothrombin time (PT), thrombin time (TT), fibrinogen, and CA-125, with the area under curve (AUC) of 0.758 (95%CI 0.717–0.800) and 0.742 (95%CI 0.699–0.785), respectively (Fig. 1A and B)
The results indicated that there was no significant difference of lost to followup rate among three Combination of D-dimer and INR (DD-INR) groups (p = 0.842)
Summary
Increasing evidence supported an association between cancer and coagulation system. We aimed to identify prognostic values of coagulation biomarkers in epithelial ovarian cancer (EOC). 4 (HE4) have been used to predict the survival of EOC patients with limited sensitivity and specificity [6]. Increasing evidence showed that hyper-coagulability and fibrinolysis had a significant relationship with tumor development, progression, and dissemination [8]. As a degradation product crosslinked by activation factor XIII and hydrolyzed by fibrinolytic enzyme, D-dimer could serve as a biomarker for activated coagulation and fibrinolysis [9, 10]. Previous studies showed that abnormal pre-treatment coagulation parameters, including D-dimer and INR, could predict poor survival in various malignancies, including colorectal, lung, and liver carcinoma [13,14,15]
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