Corrigendum: Construction and validation of a robust prognostic model based on immune features in sepsis.
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ABSTRACT:
SUBMITTER: Zheng Y
PROVIDER: S-EPMC10025525 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
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Corrigendum: Construction and validation of a robust prognostic model based on immune features in sepsis.
Zheng Yongxin Y Liu Baiyun B Deng Xiumei X Chen Yubiao Y Huang Yongbo Y Zhang Yu Y Xu Yonghao Y Sang Ling L Liu Xiaoqing X Li Yimin Y
Frontiers in immunology 20230306
[This corrects the article DOI: 10.3389/fimmu.2022.994295.]. ...[more]
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Project description:PurposeSepsis, with life-threatening organ failure, is caused by the uncontrolled host response to infection. Immune response plays an important role in the pathophysiology of sepsis. Immune-related genes (IRGs) are promising novel biomarkers that have been used to construct the diagnostic and prognostic model. However, an IRG prognostic model used to predict the 28-day mortality in sepsis was still limited. Therefore, the study aimed to develop a prognostic model based on IRGs to identify patients with high risk and predict the 28-day mortality in sepsis. Then, we further explore the circulating immune cell and immunosuppression state in sepsis.Materials and methodsThe differentially expressed genes (DEGs), differentially expressed immune-related genes (DEIRGs), and differentially expressed transcription factors (DETFs) were obtained from the GEO, ImmPort, and Cistrome databases. Then, the TFs-DEIRGs regulatory network and prognostic prediction model were constructed by Cox regression analysis and Pearson correlation analysis. The external datasets also validated the reliability of the prognostic model. Based on the prognostic DEIRGs, we developed a nomogram and conducted an independent prognosis analysis to explore the relationship between DEIRGs in the prognostic model and clinical features in sepsis. Besides, we further evaluate the circulating immune cells state in sepsis.ResultsA total of seven datasets were included in our study. Among them, GSE65682 was identified as a discovery cohort. The results of GSEA showed that there is a significant correlation between sepsis and immune response. Then, based on a P value <0.01, 69 prognostic DEIRGs were obtained and the potential molecular mechanisms of DEIRGs were also clarified. According to multivariate Cox regression analysis, 22 DEIRGs were further identified to construct the prognostic model and identify patients with high risk. The Kaplan-Meier survival analysis showed that high-risk groups have higher 28-day mortality than low-risk groups (P=1.105e-13). The AUC value was 0.879 which symbolized that the prognostic model had a better accuracy to predict the 28-day mortality. The external datasets also prove that the prognostic model had an excellent prediction value. Furthermore, the results of correlation analysis showed that patients with Mars1 might have higher risk scores than Mars2-4 (P=0.002). According to the previous study, Mars1 endotype was characterized by immunoparalysis. Thus, the sepsis patients in high-risk groups might exist the immunosuppression. Between the high-risk and low-risk groups, circulating immune cells types were significantly different, and risk score was significantly negatively correlated with naive CD4+ T cells (P=0.019), activated NK cells (P=0.0045), monocytes (P=0.0134), and M1 macrophages (P=0.0002).ConclusionsOur study provides a robust prognostic model based on 22 DEIRGs which can predict 28-day mortality and immunosuppression status in sepsis. The higher risk score was positively associated with 28-day mortality and the development of immunosuppression. IRGs are a promising biomarker that might facilitate personalized treatments for sepsis.
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Project description:Background Glioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued. Purpose Here, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM. Methods Glioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandem mass spectrometry and western blotting (WB). Results Six IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB. Conclusion Herein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research.
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Project description:BackgroundPancreatic adenocarcinoma (PAAD) is a highly lethal and aggressive tumor with poor prognoses. The predictive capability of immune-related genes (IRGs) in PAAD has yet to be explored. We aimed to explore prognostic-related immune genes and develop a prediction model for indicating prognosis in PAAD.MethodsThe messenger (m)RNA expression profiles acquired from public databases were comprehensively integrated and differentially expressed genes were identified. Univariate analysis was utilized to identify IRGs that related to overall survival. Whereafter, a multigene signature in the Cancer Genome Atlas cohort was established based on the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Moreover, a transcription factors regulatory network was constructed to reveal potential molecular processes in PAAD. PAAD datasets downloaded from the Gene Expression Omnibus database were applied for the validations. Finally, correlation analysis between the prognostic model and immunocyte infiltration was investigated.ResultsTotally, 446 differentially expressed immune-related genes were screened in PAAD tissues and normal tissues, of which 43 IRGs were significantly related to the overall survival of PAAD patients. An immune-based prognostic model was developed, which contained eight IRGs. Univariate and multivariate Cox regression revealed that the risk score model was an independent prognostic indicator in PAAD (HR > 1, P < 0.001). Besides, the sensitivity of the model was evaluated by the receiver operating characteristic curve analysis. Finally, immunocyte infiltration analysis revealed that the eight-gene signature possibly played a pivotal role in the status of the PAAD immune microenvironment.ConclusionA novel prognostic model based on immune genes may serve to characterize the immune microenvironment and provide a basis for PAAD immunotherapy.
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Project description:Sepsis is a life-threatening syndrome resulting from immune system dysfunction that is caused by infection. It is of great importance to analyze the immune characteristics of sepsis, identify the key immune system related genes, and construct diagnostic models for sepsis. In this study, the sepsis transcriptome and expression profiling data were merged into an integrated dataset containing 277 sepsis samples and 117 non-sepsis control samples. Single-sample gene set enrichment analysis (ssGSEA) was used to assess the immune cell infiltration. Two sepsis immune subtypes were identified based on the 22 differential immune cells between the sepsis and the healthy control groups. Weighted gene co-expression network analysis (WCGNA) was used to identify the key module genes. Then, 36 differentially expressed immune-related genes were identified, based on which a robust diagnostic model was constructed with 11 diagnostic genes. The expression of 11 diagnostic genes was finally assessed in the training and validation datasets respectively. In this study, we provide comprehensive insight into the immune features of sepsis and establish a robust diagnostic model for sepsis. These findings may provide new strategies for the early diagnosis of sepsis in the future.
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Project description:ObjectFocus on immune-related gene pairs (IRGPs) and develop a prognostic model to predict the prognosis of patients with lung adenocarcinoma (LUAD).MethodsFirst, the LUAD patient dataset was downloaded from The Cancer Genome Atlas database, and paired analysis of immune-related genes was subsequently conducted. Then, LASSO regression was used to screen prognostic IRGPs for building a risk prediction model. Meanwhile, the Gene Expression Omnibus database was used for external validation of the model. Next, the clinical predictive power of IRGPs features was assessed by uni-multivariate Cox regression analysis, the infiltration of key immune cells in high and low IRGPs risk groups was analyzed with CIBERSORT, quanTIseq, and Timer, and the key pathways enriched for IRGPs were assessed using the Kyoto Encyclopedia of Genes and Genomes. Finally, the expression and related functions of key immune cells and genes were verified by immunofluorescence and cell experiments of tissue samples.ResultsIt was revealed that the risk score of 19 IRGPs could be used as accurate indicators to evaluate the prognosis of LUAD patients, and the risk score was mainly related to T cell infiltration based on CIBERSORT analysis. Two genes of IRGPs, IL6, and CCL2, were found to be closely associated with the expression of PD-1/PD-L1 and the function of T-cells. Depending on the results of tissue immunofluorescence, IL6, CCL2, and T cells were highly expressed in the LUAD tissues of patients. Furthermore, IL6 and CCL2 were positively correlated with the expression of T cells. Besides, qRT-PCR assay in four different LUAD cells proved that IL6 and CCL2 were positively correlated with the expression of PD-L1 (P < .001).ConclusionsBased on 19 IRGPs, an effective prognosis model was established to predict the prognosis of LUAD patients. In addition, IL6 and CCL2 are closely related to the function of T-cells.
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Project description:Growing evidence has indicated that prognostic biomarkers have a pivotal role in tumor and immunity biological processes. TP53 mutation can cause a range of changes in immune response, progression, and prognosis of colorectal cancer (CRC). Thus, we aim to build an immunoscore prognostic model that may enhance the prognosis of CRC from an immunological perspective. We estimated the proportion of immune cells in the GSE39582 public dataset using the CIBERSORT (Cell type identification by estimating relative subset of known RNA transcripts) algorithm. Prognostic genes that were used to establish the immunoscore model were generated by the LASSO (Least absolute shrinkage and selection operator) Cox regression model. We established and validated the immunoscore model in GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) cohorts, respectively; significant differences of overall survival analysis were found between the low and high immunoscore groups or TP53 subgroups. In the multivariable Cox analysis, we observed that the immunoscore was an independent prognostic factor both in the GEO cohort (HR (Hazard ratio) 1.76, 95% CI (confidence intervals): 1.26-2.46) and the TCGA cohort (HR 1.95, 95% CI: 1.20-3.18). Furthermore, we established a nomogram for clinical application, and the results suggest that the nomogram is a better predictive model for prognosis than immunoscore or TNM staging.
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Project description:Lung adenocarcinoma (LUAD), the most common non-small-cell lung cancer, is characterized by a dense lymphocytic infiltrate, which indicates that the immune system plays an active role in the development and growth of this cancer. However, no investigations to date have proposed robust models for predicting survival outcome for patients with LUAD in terms of tumour immunology. A total of 761 LUAD patients were included in this study, in which the database of The Cancer Genome Atlas (TCGA) was utilized for discovery, and the Gene Expression Omnibus (GEO) database was utilized for validation. Bioinformatics analysis and R language tools were utilized to construct an immune prognostic model and annotate biological functions. Lung adenocarcinoma showed a weakened immune phenotype compared with adjacent normal tissues. Immune-related gene sets were profiled, an immune prognostic model based on 2 immune genes (ANLN and F2) was developed with the TCGA database to distinguish cases as having a low or high risk of unfavourable prognosis, and the model was verified with the GEO database. The model was prognostically significant in stratified cohorts, including stage I-II, stage III-IV and epidermal growth factor receptor (EGFR) mutant subsets, and was considered to be an independent prognostic factor for LUAD. Furthermore, the low- and high-risk groups showed marked differences in tumour-infiltrating leucocytes, tumour mutation burden, aneuploidy and PD-L1 expression. In conclusion, an immune prognostic model was proposed for LUAD that is capable of independently identifying patients at high risk for poor survival, suggesting a relationship between local immune status and prognosis.
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Project description:As heterogeneity of cervical squamous cell carcinoma (CSCC), prognosis assessment for CSCC patients remain challenging. To develop novel prognostic strategies for CSCC patients, associated biomarkers are urgently needed. This study aimed to cluster CSCC samples from a molecular perspective. CSCC expression data sets were obtained from The Cancer Genome Atlas and based on the accessed expression profile, a co-expression network was constructed with weighted gene co-expression network analysis to form different gene modules. Tumor microenvironment was evaluated using ESTIMATE algorithm, observing that the brown module was highly associated with tumor immunity. CSCC samples were clustered into three subtypes by consensus clustering based on gene expression profiles in the module. Gene set variation analysis showed differences in immune-related pathways among the three subtypes. CIBERSORT and single-sample gene set enrichment analysis analyses showed the difference in immune cell infiltration among subtype groups. Also, Human leukocyte antigen protein expression varied considerably among subtypes. Subsequently, univariate, Lasso and multivariate Cox regression analyses were performed on the genes in the brown module and an 8-gene prognostic model was constructed. Kaplan-Meier analysis illuminated that the low-risk group manifested a favorable prognosis, and receiver operating characteristic curve showed that the model has good predictive performance. qRT-PCR was used to examine the expression status of the prognosis-associated genes. In conclusion, this study identified three types of CSCC from a molecular perspective and established an effective prognostic model for CSCC, which will provide guidance for clinical subtype identification of CSCC and treatment of patients.
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Project description:BackgroundThough immunotherapy has become one of the standard therapies for colon cancer, the overall effective rate of immunotherapy is very low. Constructing an immune-related genes prognostic index (IRGPI) model may help to predict the response to immunotherapy and clinical outcomes.MethodsDifferentially expressed immune-related genes (DEIRGs) between normal tissues and colon cancer tissues were identified and used to construct the co-expression network. Genes in the module with the most significant differences were further analyzed. Independent prognostic immune-related genes (IRGs) were identified by univariate and multivariate cox regression analysis. Independent prognostic IRGs were used to construct the IRGPI model using the multivariate cox proportional hazards regression model, and the IRGPI model was validated by independent dataset. ROC curves were plotted and AUCs were calculated to estimate the predictive power of the IRGPI model to prognosis. Gene set enrichment analysis (GSEA) was performed to screen the enriched KEGG pathways in the high-risk and low-risk phenotype. Correlations between IRGPI and clinical characteristic, immune checkpoint expression, TMB, immune cell infiltration, immune function, immune dysfunction, immune exclusion, immune subtype were analyzed.ResultsTotally 680 DEIRGs were identified. Three independent IRGs,NR5A2, PPARGC1A and LGALS4, were independently related to survival. NR5A2, PPARGC1A and LGALS4 were used to establish the IRGPI model. Survival analysis showed that patients with high-risk showed worse survival than patients in the low-risk group. The AUC of the IRGPI model for 1-year, 3-year and 5-year were 0.584, 0.608 and 0.697, respectively. Univariate analysis and multivariate cox regression analysis indicated that IRGPI were independent prognostic factors for survival. Stratified survival analysis showed that patients with IRGPI low-risk and low TMB had the best survival, which suggested that combination of TMB and IRGPI can better predict clinical outcome. Immune cell infiltration, immune function, immune checkpoint expression and immune exclusion were different between IRGPI high-risk and low-risk patients.ConclusionAn immune-related genes prognostic index (IRGPI) was constructed and validated in the current study and the IRGPI maybe a potential biomarker for evaluating response to immunotherapy and clinical outcome for colon cancer patients.
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