title: Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study.
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.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Shu
authors.forename: Hao
authors.initials: H
authors.lastname: Weng
authors.forename: Run-Fa
authors.initials: RF
authors.lastname: Bao
authors.forename: Xiang-Song
authors.initials: XS
authors.lastname: Wu
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Xu-An
authors.initials: XA
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Xiang
authors.forename: Huai-Feng
authors.initials: HF
authors.lastname: Li
authors.forename: Mao-Lan
authors.initials: ML
authors.lastname: Li
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Mu
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Wu
authors.affiliation: 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. liuybphd@126.com.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015241:Fibrinogens, Abnormal / Q000378:metabolism*; D005706:Gallbladder Neoplasms / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D015241:Fibrinogens, Abnormal
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