ABSTRACT
Objective To construct a prognostic model for cuprotosis-related genes (CRGs) in patients with hepatocellular carcinoma (HCC). Methods Differential expression of CRGs in HCC was analyzed on the basis of datasets from the TCGA database. The potential mechanisms of CRGs and their related genes in HCC were explored through GO and KEGG enrichment analyses. The prognostic value of the CRGs was evaluated through Kaplan-Meier survival analysis, and the relationship between CRG expression and immune cell infiltration was investigated. CRGs significantly correlated with prognosis in patients with HCC were identified. A prognostic model was established through univariate, Lasso regression, and multivariate Cox regression analyses. The patients were divided into two groups by risk score. ROC curve was used in evaluating the prognostic model. The relationship of risk score or clinical factors with prognosis was analyzed through univariate and multivariate Cox regression analyses. Results A total of 11 differentially expressed CRGs in HCC were obtained. The main enriched GO item of CRGs and their related genes was oxidoreductase activity, acting on the aldehyde or oxo group of donors, and the main enriched KEGG pathway was carbon metabolism. The expression of CRGs was significantly correlated with pDC, T helper cells and other immune cells (P < 0.05). Three CRGs (CDKN2A, DLAT, and LIPT1) were screened and a prognostic model was constructed. There was significant difference in overall survival between the high- and low-risk groups (P < 0.001). The risk score is an independent risk factor for poor prognosis (P < 0.001). Conclusion The prognostic model for CRGs in patients with HCC is constructed using TCGA database data. This model may be used in evaluating patient prognosis.
ABSTRACT
OBJECTIVE To study different extraction fractions of Agrimonia pilosa against h epatic fibrosis. METHODS Using hepatic stellate cells HSC-T 6 of rats as objects ，the effects of different extraction fractions （total extract ，ethyl acetate fraction ， petroleum ether fraction and n-butanol fraction ）with different concentrations （0.5，5，50，500，5 000 μg/mL，calculated by raw drug）of A. pilosa on the proliferation of HSC-T 6 cells were detected （after treated for 24，48，72 h）；median inhibition concentration（IC50）was also caculated. Platelet-derived growth factor （PDGF-BB）was used to induce the activation of HSC-T 6 cells to establish hepatic fibrosis cell model. Flow cytometry was used to detect the effects of different extraction fractions of A. pilosa on apoptosis of HSC-T 6 cells. The expression of collagen Ⅰ（Col-Ⅰ）in the supernatant was detected by enzyme linked immunosorbent assay. The expressions of α-smooth muscle actin （α-SMA），Col-Ⅰ，B-cell lymphoma- 2（Bcl-2），Bcl-2-associated X protein （Bax）and caspase- 3 were detected by Western blot assay. RESULTS Total extract ，ethyl acetate fraction ，petroleum ether fraction and n-butanol fraction of A. pilosa could significantly increase the apoptotic rate of HSC-T 6 cells（P＜0.01）. After treated for 24 h，IC50 of above fractions were 50.17，20.75，5.82，4.09 μg/mL，respectively. After intervened with PDGF-BB ，the expression of Col- Ⅰ in supernatant of HSC-T 6 cells as well as protein expression of Col- Ⅰ，α-SMA，Bcl-2，Bax and caspase- 3 in HSC-T6 cells were increased significantly （P＜0.01）. After intervened with different extraction fractions of A. pilosa ，most of the expressions of above proteins in HSC-T 6 cell culture supernatant or cells were significantly reversed compared with PDGF-BB group （P＜0.05 or P＜0.01）， and the intervention effect of n-butanol fraction of A. pilosa was the most significant. CONCLUSIONS Different extraction fractions of A. pilosa can inhibite the proliferation of HSC-T 6 cells and induce their apoptosis；n-butanol fraction from A. pilosa may be an effective fraction to exert the effect of anti-hepatic fibrosis.