Dataset Information

Construction of immune-related gene pairs signature to predict the overall survival of osteosarcoma patients.

ABSTRACT: The purpose of this study is to establish the prognosis of osteosarcoma patients based on the characteristics of immune-related gene pairs. We used the lasso Cox regression model to construct and verify the signature consisting of 14 immune-related gene pairs. This signature can accurately predict the overall survival of osteosarcoma patients and is an independent prognostic factor for osteosarcoma patients. For this we constructed a signature-based nomogram. The results of the nomogram show that our signature can bring clinical net benefits. We then assessed the abundance of infiltrating immune cells in each sample, and combine the results of the gene set enrichment analysis of a single sample to explore the differences in the immune microenvironment between IRPG signature groups. The result of gene set enrichment analysis shows the strong relationship between signature and immune system. Finally, we evaluated the relationship between signature and immunotherapy efficiency using algorithms such as TIMI and SubMap to explore patients who might benefit from immunotherapy. In conclusion, our signature can predict the overall survival rate of osteosarcoma patients and provide potential guidance for exploring patients who may benefit from immunotherapy.

SUBMITTER: Li LQ

PROVIDER: S-EPMC7746392 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Construction of immune-related gene pairs signature to predict the overall survival of osteosarcoma patients.

Li Long-Qing LQ Zhang Liang-Hao LH Zhang Yan Y Lu Xin-Chang XC Zhang Yi Y Liu Yong-Kui YK Khader Manhas Abdul MA Jia-Wen Tao-Liu Li Jia-Zhen JZ

Aging 20201116 22

The purpose of this study is to establish the prognosis of osteosarcoma patients based on the characteristics of immune-related gene pairs. We used the lasso Cox regression model to construct and verify the signature consisting of 14 immune-related gene pairs. This signature can accurately predict the overall survival of osteosarcoma patients and is an independent prognostic factor for osteosarcoma patients. For this we constructed a signature-based nomogram. The results of the nomogram show tha ...[more]

PMID: 33203792

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Project description:BackgroundAging is the major risk factor for most human cancers. We aim to develop and validate a reliable aging-related gene pair signature (ARGPs) to predict the prognosis of gastric cancer (GC) patients.MethodsThe mRNA expression data and clinical information were obtained from two public databases, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus (GEO) dataset, respectively. The best prognostic signature was established using Cox regression analysis (univariate and least absolute shrinkage and selection operator). The optimal cut-off value to distinguish between high- and low-risk patients was found by time-dependent receiver operating characteristic (ROC). The prognostic ability of the ARGPS was evaluated by a log-rank test and a Cox proportional hazards regression model.ResultsThe 24 ARGPs were constructed for GC prognosis. Using the optimal cut-off value - 0.270, all patients were stratified into high risk and low risk. In both TCGA and GEO cohorts, the results of Kaplan-Meier analysis showed that the high-risk group has a poor prognosis (P < 0.001, P = 0.002, respectively). Then, we conducted a subgroup analysis of age, gender, grade and stage, and reached the same conclusion. After adjusting for a variety of clinical and pathological factors, the results of multivariate COX regression analysis showed that the ARGPs is still an independent prognostic factor of OS (HR, 4.919; 95% CI 3.345-7.235; P < 0.001). In comparing with previous signature, the novel signature was superior, with an area under the receiver operating characteristic curve (AUC) value of 0.845 vs. 0.684 vs. 0.695. The results of immune infiltration analysis showed that the abundance of T cells follicular helper was significantly higher in the low-risk group, while the abundance of monocytes was the opposite. Finally, we identified and incorporated independent prognostic factors and developed a superior nomogram to predict the prognosis of GC patients.ConclusionOur study has developed a robust prognostic signature that can accurately predict the prognostic outcome of GC patients.

Project description:Objectives: Ferroptosis plays vital roles in the pathogenesis of various malignant tumors. However, knowledge on roles of ferroptosis in osteosarcoma remains scarce. In the present study, a comprehensive bioinformatics analysis was performed aiming to identify ferroptosis-related genes (FRGs), construct a FRGs-based model predicting overall survival (OS), and assess the impact of these FRGs on the migration and invasion of osteosarcoma cells. Methods: Initially, data regarding differentially expressed FRGs were obtained from the GSE160881 dataset. Prognostic significance and possible biological functions of these differentially expressed FRGs were comprehensively and systematically explored adopting a series of bioinformatics methods. The impact of cystathionine β-synthase (CBS) on migration and invasion of osteosarcoma cells were assessed using transwell assays. Results: A total of 50 FRGs were differentially expressed. Four FRGs including G6PD, VEGFA, CBS, and HMOX1 were used to construct a model predicting OS in osteosarcoma patients. In the training cohort, patients with high risk had significantly poorer OS than those with low risk, which was also demonstrated in validation cohorts (GSE16091 and GSE39058). Furthermore, we established a clinically useful nomogram predicting OS using the four FRGs mentioned above. Risk scores were significantly associated with the proportion of tumor-infiltrating immune cells. Additionally, we used the Cytoscape software to identify hub FRGs, and found that TP53, HMOX1, SLC7A11, HRAS, VEGFA, and TXNRD1 were hub FRGs. By performing in vitro cell culture experiments, we demonstrated that invasion and migration capability of Saos2 and HOS cells were significantly weakened after CBS knock down. Conclusions: In conclusion, gene signatures based on four FRGs were reliable in predicting OS in patients with osteosarcoma. Findings from this study will enable a better understanding of the prognostic significance of FRGs and tumor immunity in osteosarcoma.

Project description:Background: Lung adenocarcinoma (LUAD) is a malignant tumor with high heterogeneity and poor prognosis. Ferroptosis, a form of regulated cell-death-related iron, has been proven to trigger inflammation-associated immunosuppression in the tumor microenvironment, which promotes tumor growth. Therefore, the clinical prognostic value of ferroptosis-related genes in LUAD needs to be further explored. Method: In this study, we downloaded the mRNA expression profiles and corresponding clinical data of LUAD patients from the Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct ferroptosis-related gene signature. Based on these, we established the nomograms for prognosis prediction and validated the model in the GSE72094 dataset. The cell type was identified using the CIBERSORT algorithm for estimating relative subsets of RNA transcripts, which was then used to screen significant tumor immune-infiltrating cells associated with the LUAD prognosis prediction model. Subsequently, we applied co-expression analysis to reveal the relationship between ferroptosis-related genes and significant immune cells. Results: The univariate COX regression analysis showed that 20 genes were associated with the overall survival (OS) as prognostic differentially expressed genes (DEGs) (FDR <0.05). Patients were divided into two risk groups using a 13-gene signature, with the high-risk group having a significantly worse OS than their low-risk counterparts (p < 0.001). We used receiver operating characteristic (ROC) curve analysis to confirm the predictive capacity of the signature. Besides, we identified seven pairs of ferroptosis-related genes and tumor-infiltrating immune cells associated with the prognosis of LUAD patients. Conclusion: In this study, we construct a ferroptosis-related gene signature that can be used for prognostic prediction in LUAD. In addition, we reveal a potential connection between ferroptosis and tumor-infiltrating immune cells.

Project description:Background: An imbalance in the redox homeostasis has been reported in multiple cancers and is associated with a poor prognosis of disease. However, the prognostic value of redox-related genes in non-small-cell lung cancer (NSCLC) remains unclear. Methods: RNA sequencing data, DNA methylation data, mutation, and clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Redox-related differentially expressed genes (DEGs) were used to construct the prognostic signature using least absolute shrinkage and selection operator (LASSO) regression analysis. Kaplan-Meier survival curve and receiver operator characteristic (ROC) curve analyses were applied to validate the accuracy of the gene signature. Nomogram and calibration plots of the nomogram were constructed to predict prognosis. Pathway analysis was performed using gene set enrichment analysis. The correlations of risk score with tumor stage, immune infiltration, DNA methylation, tumor mutation burden (TMB), and chemotherapy sensitivity were evaluated. The prognostic signature was validated using GSE31210, GSE26939, and GSE68465 datasets. Real-time polymerase chain reaction (PCR) was used to validate dysregulated genes in NSCLC. Results: A prognostic signature was constructed using the LASSO regression analysis and was represented as a risk score. The high-risk group was significantly correlated with worse overall survival (OS) (p < 0.001). The area under the ROC curve (AUC) at the 5-year stage was 0.657. The risk score was precisely correlated with the tumor stage and was an independent prognostic factor for NSCLC. The constructed nomogram accurately predicted the OS of patients after 1-, 3-, and 5-year periods. DNA replication, cell cycle, and ECM receptor interaction were the main pathways enriched in the high-risk group. In addition, the high-risk score was correlated with higher TMB, lower methylation levels, increased infiltrating macrophages, activated memory CD4+ T cells, and a higher sensitivity to chemotherapy. The signature was validated in GSE31210, GSE26939, and GSE68465 datasets. Real-time PCR validated dysregulated mRNA expression levels in NSCLC. Conclusions: A prognostic redox-related gene signature was successfully established in NSCLC, with potential applications in the clinical setting.

Dataset Information

Construction of immune-related gene pairs signature to predict the overall survival of osteosarcoma patients.

Publications

Construction of immune-related gene pairs signature to predict the overall survival of osteosarcoma patients.

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