Identification of immune cell-related prognostic genes characterized by a distinct microenvironment in hepatocellular carcinoma

BACKGROUND The development and progression of hepatocellular carcinoma(HCC)have been reported to be associated with immune-related genes and the tumor microenvir-onment.Nevertheless,there are not enough prognostic biomarkers and models available for clinical use.Based on seven prognostic genes,this study calculated overall survival in patients with HCC using a prognostic survival model and revealed the immune status of the tumor microenvironment(TME).AIM To develop a novel immune cell-related prognostic model of HCC and depict the basic profile of the immune response in HCC.METHODS We obtained clinical information and gene expression data of HCC from The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)datasets.TCGA and ICGC datasets were used for screening prognostic genes along with developing and validating a seven-gene prognostic survival model by weighted gene coexpression network analysis and least absolute shrinkage and selection operator regression with Cox regression.The relative analysis of tumor mutation burden(TMB),TME cell infiltration,immune check-points,immune therapy,and functional pathways was also performed based on prognostic genes.RESULTS Seven prognostic genes were identified for signature construction.Survival receiver operating characteristic curve analysis showed the good performance of survival prediction.TMB could be regarded as an independent factor in HCC survival prediction.There was a significant difference in stromal score,immune score,and estimate score between the high-risk and low-risk groups stratified based on the risk score derived from the seven-gene prognostic model.Several immune checkpoints,including VTCN1 and TNFSF9,were found to be associated with the seven prognostic genes and risk score.Different combinations of checkpoint blockade targeting inhibitory CTLA4 and PD1 receptors and potential chemotherapy drugs hold great promise for specific HCC therapies.Potential pathways,such as cell cycle regulation and metabolism of some amino acids,were also identified and analyzed.CONCLUSION The novel seven-gene(CYTH3,ENG,HTRA3,PDZD4,SAMD14,PGF,and PLN)prognostic model showed high predictive efficiency.The TMB analysis based on the seven genes could depict the basic profile of the immune response in HCC,which might be worthy of clinical application.

The role of baicalin on carbon tetrachloride induced liver fibrosis

The effect of the baicalin,a bio-active flavonoid extracted from Scutellaria baicalensis Georgi,on the carbon tetrachloride(CCl_(4))induced liver fibrosis was investigated.To compare the effect of baicalin on the liver fibrosis,five different groups of rats treated by 100,200,and 400 mg/kg baicalin were studied.Upon CCl_(4) treatment,the levels of procollagen type III,aspartate aminotransferase,aminotransferase,hyaluronic acid,and hydroxyproline were significantly increased,whereas the superoxide dismutase and glutathione peroxidase content were decreased.These changes in the biochemical parameters,which are associated with liver function,were significantly attenuated by the baicalin treatment,suggesting that baicalin can suppress the liver fibrosis induced by CCl_(4).Moreover,the histological staining analysis demonstrated that baicalin could effectively inhibit the degree of liver cell injury.The protein expression of AKT/JAK2/ERK in the serum were markedly increased by CCl_(4) but suppressed by the treatment of baicalin in a dose-dependent manner,implying that baicalin can attenuated cell apoptosis induced by CCl_(4).Overall,these results suggest that baicalin effectively protects hepatocytes from the CCl_(4) oxidative damage,likely due to the inhibition of free radical generation and cell apoptosis during the liver injury.