Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway

Abstract

Aim: Hyperfibrinogenemia had been widely observed in various cancer patients, however, whether fibrinogen (FIB) influences the survival outcome of patients with primary liver cancer (PLC) remains unknown. This study was aimed to evaluate the predictive value of preoperative FIB in the survival outcome of PLC patients and explore the possible mechanism. Methods: Retrospective study was performed in PLC patients who underwent hepatectomy. Logistic regression analysis was used to explore the independent risk factors of the overall survival (OS) of PLC patients. The predictive value of FIB for the survival outcome was analyzed by Kaplan-Meier method, receiver operating characteristic curve and Cox proportional hazard model combined with B-splines. Hepatoma cell migration and invasion were detected by wound healing assay and Transwell assay, protein expression was measured by Western blot. mTOR inhibitor and PTEN overexpression plasmid were used to confirm the involvement of the PTEN/AKT/mTOR pathway during FIB treatment. Results: Preoperative FIB was confirmed to be related with the OS in PLC patients, higher FIB (>2.5 g/L) indicated higher hazard ratio. Meanwhile, FIB could promote hepatoma cell migration and invasion through the activation of AKT/mTOR pathway and epithelial-mesenchymal transformation (EMT). Moreover, the promotion of FIB on cell migration and invasion could be inhibited by mTOR inhibitor and PTEN overexpression. Conclusions: Preoperative FIB could be related with the prognosis of PLC patients, the risk of death in PLC patients gradually increases along with the up-regulation of FIB. FIB may promote hepatoma metastasis by inducing EMT via the activation of PTEN/AKT/mTOR pathway.

Keywords

• Fibrinogen
• Primary liver cancer
• Survival
• Epithelial-mesenchymal transition
• PTEN/AKT/mTOR pathway