摘要
Aim:Pneumonia is the most frequent early postoperative complication in liver transplantation(LT)recipients.Inflammation may provide a favorable environment for tumor implantation,so we aimed to evaluate the impact of pneumonia on pulmonary metastasis of hepatocellular carcinoma(HCC)and reveal its underlying mechanism.Methods:A training cohort with 234 LT recipients were recorded and analyzed.Using the propensity-score method,we matched covariates between patients with and without pneumonia.A model for predicting pulmonary metastasis was built and validated in an independent validating cohort containing 179 subjects.A mouse model was built to mimic HCC pulmonary metastasis.The potential pathway was revealed by cytokine array analysis and validated in vitro.Results:Pneumonia was an independent risk factor for pulmonary metastasis in liver transplant recipients.It promoted pulmonary metastasis in both the clinical setting and the mouse model.In vitro,LPS-stimulated VEGF secretion from macrophages in the lung significantly reduced cell apoptosis and activated PI3K/AKT/cas-9 signaling.Administration of VEGF receptor2 inhibitor Vatalanib could reduce metastasis and improve prognosis in pneumonia mice.Conclusion:Pneumonia promotes HCC pulmonary metastasis by activating PI3K/AKT/Cas-9 signaling in HCC cells via macrophage-originated VEGF.Vatalanib might be efficient in reducing HCC pulmonary metastasis in liver transplant recipients with pneumonia.
基金
supported by Grant Zhejiang Provincial Natural Science Foundation of China(LQ22H160052)
National Natural Science Foundation of China(82300742)
The Major Research Plan of the National Natural Science Foundation of China(92159202).
