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Open Access Research article

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

Yi-Jun Shu12, Hao Weng12, Run-Fa Bao12, Xiang-Song Wu12, Qian Ding12, Yang Cao12, Xu-An Wang12, Fei Zhang12, Shan-Shan Xiang12, Huai-Feng Li12, Mao-Lan Li12, Jia-Sheng Mu12, Wen-Guang Wu12 and Ying-Bin Liu12*

Author Affiliations

1 Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affliated with Shanghai Jiao Tong University, School of Medicine, No.1665 Kongjiang Road, Shanghai 200092, China

2 Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China

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BMC Cancer 2014, 14:566  doi:10.1186/1471-2407-14-566

Published: 5 August 2014

Abstract

Background

Coagulation 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.

Methods

We 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.

Results

The 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.

Conclusions

Preoperative 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.

Keywords:
Gallbladder cancer; Coagulation assays; Hyperfibrinogenemia; Prognosis