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

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 outco...

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Main Authors: Xuemeng Qian, Jiajing Cai, Qi Qi, Jia Han, Xinfang Zhu, Rong Xia, Qi Zhang
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023039038
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author Xuemeng Qian
Jiajing Cai
Qi Qi
Jia Han
Xinfang Zhu
Rong Xia
Qi Zhang
author_facet Xuemeng Qian
Jiajing Cai
Qi Qi
Jia Han
Xinfang Zhu
Rong Xia
Qi Zhang
author_sort Xuemeng Qian
collection DOAJ
description 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.
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spelling doaj.art-3832230f84024acfa4bd43cc6fad051f2023-06-02T04:23:36ZengElsevierHeliyon2405-84402023-06-0196e16696Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathwayXuemeng Qian0Jiajing Cai1Qi Qi2Jia Han3Xinfang Zhu4Rong Xia5Qi Zhang6Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaCorresponding author. Department of Transfusion Medicine, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, PR China.; Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaCorresponding author. Department of Transfusion Medicine, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, PR China.; Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaAim: 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.http://www.sciencedirect.com/science/article/pii/S2405844023039038FibrinogenPrimary liver cancerSurvivalEpithelial-mesenchymal transitionPTEN/AKT/mTOR pathway
spellingShingle Xuemeng Qian
Jiajing Cai
Qi Qi
Jia Han
Xinfang Zhu
Rong Xia
Qi Zhang
Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway
Heliyon
Fibrinogen
Primary liver cancer
Survival
Epithelial-mesenchymal transition
PTEN/AKT/mTOR pathway
title Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway
title_full Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway
title_fullStr Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway
title_full_unstemmed Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway
title_short Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway
title_sort preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the pten akt mtor pathway
topic Fibrinogen
Primary liver cancer
Survival
Epithelial-mesenchymal transition
PTEN/AKT/mTOR pathway
url http://www.sciencedirect.com/science/article/pii/S2405844023039038
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