Objective To analyze the immune genome environment of colon adenocarcinoma (COAD), find the immune genes related to the prognosis of COAD patients, and construct a prognostic risk score model to provide a basis for prognosis evaluation and individual diagnosis and treatment of COAD patients. Methods The RNA-seq data and clinical data of COAD patients were downloaded from TCGA (The Cancer Genome Atlas) database. Samples were divided into Tumor group and Normal group according to the type of tissues, and the differentially expressed immune genes were screened by R language. The immune genes related to the prognosis of COAD patients were screened by Cox regression analysis, and the prognostic risk score model was constructed. The COAD patients were divided into high-risk group and low-risk group according to their median risk score. The predictive efficiency of the immune gene prognosis model was evaluated by Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) curve, and the correlation between immune gene prognostic risk model and the immune cell infiltration was analyzed. Results A total of 220 differentially expressed immune genes existed in Tumor group and Normal group. By Cox univariate and multivariate regression analysis, seven prognosis-related immune genes were screened, i.e. CXCL5 (C-X-C motif Chemokine Ligand 5), IGHV5-51 (Immunoglobulin Heavy Variable 5-51), IGKV1-33 (Immunoglobulin Kappa Variable 1-33), CHGA (Chromogranin A), UCN (Urocortin), VIP (Vasoactive Intestinal Peptide) and NR3C2 (Nuclear Receptor subfamily 3 group C member 2). The overall survival rate of COAD patients was higher in low-risk group than in high-risk group (P<0.001). The overall 5-year survival rate in high-risk group and low-risk group were 49.4% and 75.8%, respectively. ROC curve showed that AUC was 0.741, suggesting that the immune gene prognosis model had a good predictive efficiency, and was associated with immune cell infiltration of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages and natural killer cells. Conclusions An immune gene risk score model has been constructed, The importance of such a prognostic model is systematically evaluated and verified in individualized treatment of patients with colon adenocarcinoma, so as to provide a direction for finding new immunotherapy targets.

OBJECTIVE: To investigate the effects of Birinapant on hepatocellular carcinoma cells and its related molecular mechanisms. METHODS: Human hepatocellular carcinoma cells QGY-7701 were treated with 0, 1, 5, 25 and 125 nmol/L Birinapant for 24, 48 and 72 hours respectively, each experiment 3 wells.The proliferation activity of cells, the apoptosis levels, the cells nuclear type, the mitochondrial membrane potential, the transcription and expression levels of genes and the cytotoxicity of Birinapant were analyzed.At the same time, 4-week-old male BALB/C mice were randomly divided into 5 groups, with 20 mice in each group.The mice were inguinal injected with QGY-7701 cells, and then subcutaneous injected with Birinapant (concentrations ranging from 0, 1, 5, 25, 125 μg/kg) in each group after two days, once every other day.On 18 day since first Birinapant injection, 10 mice were killed in each group to weigh tumor tissue and survival time was recorded from the remaining 10 mice.The effects of Birinapant on the growth of the tumor and the survival time of tumor-bearing mice were observed. RESULTS: Compared with the negative control (NC) group, the proliferation activity of QGY-7701 was inhibited significantly after Birinapant treatment and the apoptosis levels were increased significantly (<0.01).The cell mitochondrial membrane potential was decreased and the karyotype was changed (<0.01).At the same time, the transcription and expression levels of genes cellular inhibitor of apoptosis protein 1(cIAP-1), cellular inhibitor of apoptosis protein 2(cIAP-2), ras, raf, mek and erk were significantly decreased (<0.01), while the expression levels of caspase-3 and caspase-9 genes were up-regulated (<0.01).Compared with the model group (MG), the growth of the tumor was inhibited significantly and the survival time of the tumor-bearing mice was prolonged after Birinapant treatment (<0.01). CONCLUSIONS Birinapant can inhibit the expression of cIAP-1, cIAP-2 and the proteins of Ras-Raf-MEK-ERK signal pathways, so as to activate the mitochondria mediated endogenous apoptosis pathway.Birinapant shows a certain inhibitory effect on liver cancer.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Dipeptides ; Humans ; Indoles ; Liver Neoplasms ; Male ; Mice ; Mice, Inbred BALB C ; Mitochondrial Proteins