Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study

Abstract

BackgroundCoagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection.MethodsWe retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration.ResultsThe plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen.ConclusionsPreoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition.

Plasma fibrinogen level may be a possible marker for the clinical response and prognosis of patients with breast cancer receiving neoadjuvant chemotherapy

“…7,25,26 Fibrinogen can regulate cellular adhesion, proliferation, and migration through interactions with fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF). 27 By increasing the expression of vimentin and reducing the expression of E-cadherin, Shu et al 17 demonstrated that highly concentrated fibrinogen induced epithelial-mesenchymal transition (EMT), which confers migration, invasion, and metastatic capacity and multidrug resistance to tumor cells. 28,29 Fibrinogen may act as ligands for integrin and non-integrin receptors, which were found on tumor cells, stromal cells, and inflammatory cells.…”

“…4,6 Fibrinogen has recently been shown to play vital roles in tumorigenesis and contributed to angiogenesis, stroma formation, and hematogenous metastasis of tumor cells. [7][8][9][10] Elevated plasma fibrinogen level is related with tumor progression and other poor outcomes in several types of malignancies, for example, covered esophageal cancer, 11 gastric cancer, 12 pancreatic cancer, 13 colon cancer, 14 lung cancer, 15 hepatocellular cancer, 16 gallbladder cancer, 17 and gynecological cancer. [18][19][20][21] For operable breast cancer patients, elevated preoperative plasma fibrinogen level is demonstrated to be associated with cancer progression and is independently associated with a poor prognosis in patients.…”

A cumulative score based on preoperative fibrinogen and the neutrophil&ndash;lymphocyte ratio to predict outcomes in resectable gastric cancer

“…In addition, fibrinogen, a 340 kD liver glycoprotein, has been shown to play an essential role in both systemic inflammatory responses and tumor progression 10,11. Many investigators have demonstrated the clinical utility of fibrinogen as a prognostic predictor in various types of malignancies 12,13. Recently, a new scoring system combining preoperative fibrinogen and the NLR (F-NLR) has been demonstrated as a promising prognostic marker for esophageal squamous cell carcinoma 14,15.…”

Hyperfibrinogenemia predicts poor prognosis in patients with advanced biliary tract cancer

“…Recently, links between hyperfibrinogenemia and malignancies such as breast, gastric, lung, colorectal, pancreatic, and endometrial cancers have been increasingly recognized [14][15][16][17][24][25][26]. A previous retrospective study demonstrated that the preoperative plasma fibrinogen level was an independent marker of poor prognosis in gallbladder cancer patients following surgical resection [19]; however, no data have been reported on the clinicopathological and prognostic value of baseline plasma fibrinogen concentrations in patients with BTC. To the best of our knowledge, this is the first report that the plasma fibrinogen concentration at the time of diagnosis is an independent prognostic factor in patients with ABTC.…”

“…Furthermore, our unpublished data indicate that changes in plasma fibrinogen concentration before and after surgery are significantly correlated with survival in gastric cancer patients undergoing D2 curative surgery. A newly published study reported that the preoperative plasma fibrinogen level was associated with tumor progression in gallbladder cancer patients following surgical resection [19]. However, the relationship between plasma fibrinogen concentration and clinical outcomes in patients with resectable and unresectable BTC is still unknown.…”