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A prognostic risk model based on immune-related genes predicts overall survival of patients with hepatocellular carcinoma.

ABSTRACT: Background and aims:Hepatocellular carcinoma (HCC) is one of the most common heterogeneous tumors that occurs after chronic liver diseases and hepatitis virus infection. Immune-related genes (IRGs) and their ligands regulate the homeostasis of tumor microenvironment, which is essential for the treatment of HCC and its prognosis. This study aimed to investigate the clinical value of IRGs in predicting the prognosis of HCC. Methods:We downloaded RNA-seq data and clinical information from TCGA database. Samples were randomly divided into training cohort and testing cohort. The "limma" R package was performed to identify differentially expressed IRGs (DEIRGs) between HCC group and normal group. Prognostic DEIRGs (PDEIRGs) were obtained by univariate Cox analysis. LASSO and multivariate Cox analysis were used, and a prognostic risk model was constructed. In order to better demonstrate the clinical value of our model in predicting overall survival rate, a nomogram was constructed. To further investigate the molecular mechanism of our model, gene set enrichment analysis (GSEA) was performed. Results:Compared with the low-risk group, the high-risk group had a significantly worse prognosis. Moreover, our prognostic risk model can accurately stratify tumor grade and TNM stage. Importantly, in our model, not only immune checkpoint genes were well predicted, but also human leucocyte antigen-I molecules were revealed. GSEA suggested that "MAPK signaling pathway," "mTOR signaling pathway," "NOD like receptor signaling pathway," "Toll like receptor signaling pathway," "VEGF signaling pathway," "WNT signaling pathway" had significant correlations with the high-risk group. Conclusion:Overall, our study showed that our prognostic risk model can be used to assess prognosis of HCC, which may provide a certain basis for the survival rate of patients with HCC.

SUBMITTER: Pan B

PROVIDER: S-EPMC7654629 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A prognostic risk model based on immune-related genes predicts overall survival of patients with hepatocellular carcinoma.

Pan Banglun B Liu Lin L Li Wei W

Health science reports 20201110 4

<h4>Background and aims</h4>Hepatocellular carcinoma (HCC) is one of the most common heterogeneous tumors that occurs after chronic liver diseases and hepatitis virus infection. Immune-related genes (IRGs) and their ligands regulate the homeostasis of tumor microenvironment, which is essential for the treatment of HCC and its prognosis. This study aimed to investigate the clinical value of IRGs in predicting the prognosis of HCC.<h4>Methods</h4>We downloaded RNA-seq data and clinical information ...[more]

PMID: 33204848

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Project description:BackgroundHepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear.MethodsBased on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset.ResultsA total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours.ConclusionOur IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.

Project description:ObjectiveIn the development of immunotherapies in gliomas, the tumor microenvironment (TME) needs to be investigated. We aimed to construct a prognostic microenvironment-related immune signature via ESTIMATE (PROMISE model) for glioma.MethodsStromal score (SS) and immune score (IS) were calculated via ESTIMATE for each glioma sample in the cancer genome atlas (TCGA), and differentially expressed genes (DEGs) were identified between high-score and low-score groups. Prognostic DEGs were selected via univariate Cox regression analysis. Using the lower-grcade glioma (LGG) data set in TCGA, we performed LASSO regression based on the prognostic DEGs and constructed a PROMISE model for glioma. The model was validated with survival analysis and the receiver operating characteristic (ROC) in TCGA glioma data sets (LGG, glioblastoma multiforme [GBM] and LGG+GBM) and Chinese glioma genome atlas (CGGA). A nomogram was developed to predict individual survival chances. Further, we explored the underlying mechanisms using gene set enrichment analysis (GSEA) and Cibersort analysis of tumor-infiltrating immune cells between risk groups as defined by the PROMISE model.ResultsWe obtained 220 upregulated DEGs and 42 downregulated DEGs in both high-IS and high-SS groups. The Cox regression highlighted 155 prognostic DEGs, out of which we selected 4 genes (CD86, ANXA1, C5AR1, and CD5) to construct a PROMISE model. The model stratifies glioma patients in TCGA as well as in CGGA with distinct survival outcome (P<0.05, Hazard ratio [HR]>1) and acceptable predictive accuracy (AUCs>0.6). With the nomogram, an individualized survival chance could be predicted intuitively with specific age, tumor grade, Isocitrate dehydrogenase (IDH) status, and the PROMISE risk score. ROC showed significant discrimination with the area under curves (AUCs) of 0.917 and 0.817 in TCGA and CGGA, respectively. GSEA between risk groups in both data sets were significantly enriched in multiple immune-related pathways. The Cibersort analysis highlighted four immune cells, i.e., CD 8 T cells, neutrophils, follicular helper T (Tfh) cells, and Natural killer (NK) cells.ConclusionsThe PROMISE model can further stratify both LGG and GBM patients with distinct survival outcomes.These findings may help further our understanding of TME in gliomas and shed light on immunotherapies.

Project description:BackgroundDysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apoptosis-related genes (ARGs) in HCC have not been elucidated.MethodsTo screen for differentially expressed ARGs, the expression levels of 161 ARGs from The Cancer Genome Atlas (TCGA) database ( https://cancergenome.nih.gov/ ) were analyzed. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to evaluate the underlying molecular mechanisms of differentially expressed ARGs in HCC. The prognostic values of ARGs were established using Cox regression, and subsequently, a prognostic risk model for scoring patients was developed. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value of the model.ResultsCompared with normal tissues, 43 highly upregulated and 8 downregulated ARGs in HCC tissues were screened. GO analysis results revealed that these 51 genes are indeed related to the apoptosis function. KEGG analysis revealed that these 51 genes were correlated with MAPK, P53, TNF, and PI3K-AKT signaling pathways, while Cox regression revealed that 5 ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were associated with prognosis and were, therefore, obtained to develop the prognostic model. Based on the median risk scores, patients were categorized into high-risk and low-risk groups. Patients in the low-risk groups exhibited significantly elevated 2-year or 5-year survival probabilities (p < 0.0001). The risk model had a better clinical potency than the other clinical characteristics, with the area under the ROC curve (AUC = 0.741). The prognosis of HCC patients was established from a plotted nomogram.ConclusionBased on the differential expression of ARGs, we established a novel risk model for predicting HCC prognosis. This model can also be used to inform the individualized treatment of HCC patients.

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A prognostic risk model based on immune-related genes predicts overall survival of patients with hepatocellular carcinoma.

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A prognostic risk model based on immune-related genes predicts overall survival of patients with hepatocellular carcinoma.

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