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OBJECTIVE@#To establish an immune gene prognostic model of acute myeloid leukemia (AML) and explore its correlation with immune cells in bone marrow microenvironment.@*METHODS@#Gene expression profile and clinical data of TCGA-AML were downloaded from TCGA database. Immune genes were screened by LASSO analysis to construct prognosis prediction model, and prediction accuracy of the model was quantified by receiver operating characteristic curve and area under the curve. Survival analysis was performed by Log-rank test. Enriched pathways in the different immune risk subtypes were evaluated from train cohort. The relationship between immune prediction model and bone marrow immune microenvironment was verified by flow cytometry in the real world.@*RESULTS@#Patients with low-risk score of immune gene model had better prognosis than those with high-risk score. Multivariate analysis showed that the immune gene risk model was an independent prognostic factor. The risk ratio for AML patients in the training concentration was HR=24.594 (95%CI: 6.180-97.878), and the AUC for 1-year, 3-year, and 5-year overall survival rate was 0.811, 0.815, and 0.837, respectively. In addition, enrichment analysis of differential gene sets indicated activation of immune-related pathways such as cytokines and chemokines as well as autoimmune disease-related pathways. At the same time, real world data showed that patients with high immune risk had lower numbers of CD8+T cells and B lymphocytes compared with low immune risk patients.@*CONCLUSION@#We constructed a stable prognostic model for AML, which can not only predict the prognosis of AML, but also reveal the dysregulation of immune microenvironment.
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Humans , Leukemia, Myeloid, Acute/genetics , Prognosis , ROC Curve , Risk Factors , Transcriptome , Tumor Microenvironment/geneticsABSTRACT
Objective To identify the potential prognostic biomarkers of the immune-related genes signature for patients with hepatocellular carcinoma (HCC). Methods Original HCC data were downloaded from TCGA, and the immune activity of each sample was calculated by ssGSEA. HCC samples were divided into high and low immune cell infiltration groups by "GSVA" package and "hclust" package. The ESTIMATE algorithm scored the tumor microenvironment in each HCC sample. The "limma" package and Venn diagram identified effective immune-related genes. Univariate Cox, Lasso regression and multivariate Cox regression analyses were used to explore key genes. The "rms" package was used to create nomograms and draw calibration curves. Results Compared with the high immune cell infiltration group, the tumor purity of the samples in the low immune cell infiltration group was higher, the immune score, ESTIMATE score and stromal score were lower. In the high immune cell infiltration group, the immune components were more abundant, and the expression levels of TIGIT, PD-L1, PD-1, LAG3, TIM-3, CTLA4 and HLA family were higher. Multivariate Cox regression analysis showed that four immune-related genes (S100A9, HMOX1, IL18RAP and FCER1G) were used to construct the prognosis model. Compared with other clinical features, the risk score of this prognostic model was recognized as an independent prognostic factor. Conclusion This study identified the immune-related core genes which may be used in targeted therapy and immunotherapy of HCC.
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Objective:To study the relationship between differential expression of immune-related genes in breast cancer and tumor prognosis, and to find potential immunotherapy targets.Methods:Breast cancer transcriptome and the clinical data corresponding to the patient were downloaded from the TCGA database, bioinformatics methods were used to screen out the differentially expressed genes in cancer tissues, ImmPort database was combined to screen out the immunity closely related to the overall survival of the patient Gene, and COX regression was used to construct a risk scoring model for prognostic evaluation and evaluates its predictive ability.Results:A total of 2499 differentially expressed genes were found in breast cancer and adjacent tissues, and 138 differentially expressed immune-related genes were further screened. Single-factor COX analysis showed that 9 immune genes were related to prognosis, and multi-factor COX analysis screened 6 immune-related genes as independent risk factors for prognosis to construct a risk scoring model. COX regression analysis of clinical characteristics showed that the patient's risk value was an independent prognostic factor ( P<0.05) . Conclusions:There are multiple differentially expressed immune genes in breast cancer. These genes are closely related to the prognosis of patients. The risk scoring model constructed based on these immune genes can effectively predict the prognosis of patients and provide new potential therapeutic targets for breast cancer immunotherapy.
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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.
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White spot syndrome virus (WSSV), is the most contagious pathogen of cultured shrimp that causes mass mortality, leading to huge economic loss to the shrimp industry. The lack of effective therapeutic or prophylactic measures has aggravated the situation, necessitating the development of antiviral drugs. With this objective, the antiviral activity of the drug, (MP07X -derived from the marine plant) in the host, Litopenaeus vannamei was evaluated. The biochemical changes aggravated by WSSV in the host, and the in vivo efficacy of the drug in the host – pathogen interaction were analyzed. The survival percentage of the treated (with MP07X) WSSV infected host was 85 %. Significant results were obtained from the cytotoxicity assays of the drug in both the brine shrimp and host. A total of 9 biochemical parameters such as, total protein, total carbohydrate, total glucose, total free amino acid, total fatty acid, fructose 1, 6 diphosphatase, aldolase, glucose 6 phosphatase and glucose 6 phosphate dehydrogenase were examined for healthy (NEG), WSSV infected (POS) and test sample (TS) shrimps. Significant differences (p < 0.01) were observed between the POS, NEG and TS in the biochemical variables at different time intervals post infection with WSSV. In the case of POS, significantly (p < 0.01) reduced variables were observed when compared to the NEG. In contrast, significant (p < 0.01) elevations were observed in the TS after a certain time interval due to the anti-WSSV activity of MP07X. Neither the VP 28 gene nor the immediate early genes (ie 1) were expressed in the host at the 42nd and 84th hrs. Thus, in accordance with the above results it can be concluded that acute WSSV infection triggers alterations in biochemical parameters in L. vannamei and at the same time the drug is efficient enough to combat the deadly virus and can increase the survivability of the host.
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Mice was stimulated by peptidoglycan from Lactobacillus sp and detect cytokines production。It was found that PG induced the production of inflammatory cytokines (IL-1,TNF-? in peritoneal macrophages,IFN-? in spleen cell)and did not induce the IL-2 production in spleen cell. Affymetrix MOE430A genechip was used to analyze changed gene expression of immune cells. It was found that expression of cytokines and related genes were changed under peptidoglycan administration. This might induced by activation of TLR-NF-?B signal pathway.
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We have studied the effects of B7-1 on antitumor immunity induced in vivo by murine B7-1 gene transfected EL-4 lymphoma. At a lethal dose of wild - type(wt) or plasmid controlled (pc) B7-1 negative tumor cells. B7-1 gone transfected EL-4 cells inoculated in syngeneic mice were regressed. In contrast to the mice immunized with B7-1 tumor cells, immunization of mice with B7-l~EL-4 tumor cells showed significant protective effects against the sequence rechallenge of wt EL-4 tumor. Vaccination with X-irradiated B7-1 positive tumor cells at the early stage ( 7 days) after inoculation of wt EL-4 tumor cells showed some therapeutically effects but not at the late stage (14 days after inoculation). Vaccination with B7-l~+ EL-4 tumor cells delayed the occurrence of wt EL-4 tumors and prolonged the survival period of tumor-bearing mice. Our results indicate that the transfcction of B7-1 into tumor cells can increase the immunogenicity of EL-4 tumor and improve host response to wt EL-4 lymphoma. Immunization with B7-1 positive tumors can elicit effective antitumor immunity.