Objective. Bladder cancer (BC) is the most common malignancy in the urinary system and is prone to recurrence and metastasis. Pyroptosis is a kind of cell necrosis that is triggered by the gasdermin protein family. lncRNAs are noncoding RNAs that are more than 200 nucleotides long. Both pyroptosis and lncRNAs are associated with tumor development and progression. This study is aimed at exploring and establishing a prognostic signature of BC based on pyroptosis-related lncRNAs. Methods. In this study, The Cancer Genome Atlas (TCGA) database provided us with the RNA sequencing transcriptome data of bladder cancer patients, and we identified differentially expressed pyroptosis-related lncRNAs in bladder cancer. Then, the prognostic significance of these lncRNAs was assessed using univariate Cox regression analysis and LASSO regression analysis. Subsequently, 4 pyroptosis-related lncRNAs, namely, AL121652.1, AL161729.4, AC007128.1, and AC124312.3, were identified by multivariate Cox regression analysis, thus constructing the prognostic risk model. Then, we compared the levels of immune infiltration, differences in cell function, immune checkpoints, and m6A-related gene expression levels between the high- and low-risk groups. Result. Patients were divided into low-risk or high-risk groups based on the median risk score. Kaplan–Meier survival analysis indicated that the overall survival of bladder cancer patients in the low-risk group was substantially superior to that in the high-risk group ( p < 0.001 ). The receiver operating characteristic (ROC) curve further confirmed the credibility of our model. Moreover, gene set enrichment analysis (GSEA) indicated that these were different signal pathways significantly enriched between the two groups. Immune infiltration, immune checkpoint, and N6-methyladenosine-related gene analysis also reflected that there were notable differences between the two groups. Conclusion. Therefore, this prognostic risk model is based on the level of pyroptotic lncRNAs, which is conducive to individualized assessment of the risk of patients and provides a reference for clinical treatment. This will also help provide insights into the prognosis and treatment of bladder cancer.
Background: As an epigenetic alteration, DNA methylation plays an important role in early Wilms tumorigenesis and is possibly used as marker to improve the diagnosis and classification of tumor heterogeneity.Methods: Methylation data, RNA-sequencing (RNA-seq) data, and corresponding clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The prognostic values of DNA methylation subtypes in Wilms tumor were identified.Results: Four prognostic subtypes of Wilms tumor patients were identified by consensus cluster analysis performed on 312 independent prognostic CpG sites. Cluster one showed the best prognosis, whereas Cluster two represented the worst prognosis. Unique CpG sites identified in Cluster one that were not identified in other subtypes were assessed to construct a prognostic signature. The prognostic methylation risk score was closely related to prognosis, and the area under the curve (AUC) was 0.802. Furthermore, the risk score based on prognostic signature was identified as an independent prognostic factor for Wilms tumor in univariate and multivariate Cox regression analyses. Finally, the abundance of B cell infiltration was higher in the low-risk group than in the high-risk group, based on the methylation data.Conclusion: Collectively, we divided Wilms tumor cases into four prognostic subtypes, which could efficiently identify high-risk Wilms tumor patients. Prognostic methylation risk scores that were significantly associated with the adverse clinical outcomes were established, and this prognostic signature was able to predict the prognosis of Wilms tumor in children, which may be useful in guiding clinicians in therapeutic decision-making. Further independent studies are needed to validate and advance this hypothesis.
Wilms tumor (WT) is a common pediatric renal cancer, with a poor prognosis and high-risk recurrence in some patients. The inflammatory microenvironment is gradually gaining attention in WT. In this study, novel inflammation-related signatures and prognostic model were explored and integrated using bioinformatics analysis. The mRNA profile of pediatric patients with WT and inflammation-related genes (IRGs) were acquired from Therapeutically Available Research to Generate Effective Treatments (TARGET) and Gene Set Enrichment Analysis (GSEA) databases, respectively. Then, a novel prognostic model founded on 7-IRGs signature (BICC1, CSPP1, KRT8, MYCN, NELFA, NXN, and RNF113A) was established by the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression to stratify pediatric patients with WT into high- and low-risk groups successfully. And a stable performance of the prognostic risk model was verified in predicting overall survival (OS) by receiver-operating characteristic (ROC) curves, Kaplan-Meier (KM) curves, and independent prognostic analysis ( p < 0.05 ). In addition, a novel nomogram integrating risk scores with good robustness was developed and validated by C -index, ROC, and calibration plots. The potential function and pathway were explored via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA, with mainly inflammation and immune-related biological processes. The higher-risk scores, the lower immune infiltration, as shown in the single-sample GSEA (ssGSEA) and tumor microenvironment (TME) analysis. The drug sensitivity analysis showed that regulating 7-IRGs signature has a significant correlation with the chemotherapy drugs of WT patients. In summary, this study defined a prognostic risk model and nomogram based on 7-IRGs signature, which may provide novel insights into clinical prognosis and inflammatory study in WT patients. Besides, enhancing immune infiltration based on inflammatory response and regulating 7-IRGs signature are beneficial to ameliorating the efficacy in WT patients.
Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan–Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration–approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.
Background Inflammation and long noncoding RNAs (lncRNAs) are gradually becoming important in the development of bladder cancer (BC). Nevertheless, the potential of inflammatory response-related lncRNAs (IRRlncRNAs) as a prognostic signature remains unexplored in BC. Methods The Cancer Genome Atlas (TCGA) provided RNA expression profiles and clinical information of BC samples, and GSEA Molecular Signatures database provided 1171 inflammation-related genes. IRRlncRNAs were identified using Pearson correlation analysis. After that, consensus clustering was performed to form molecular subtypes. After performing least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, a risk model constructed based on the prognostic IRRlncRNAs was validated in an independent cohort. Kaplan–Meier (KM) analysis, univariate and multivariate Cox regression, clinical stratification analysis, and time-dependent receiver operating characteristic (ROC) curves were utilized to assess clinical effectiveness and accuracy of the risk model. In clusters and risk model, functional enrichment was investigated using GSEA and GSVA, and immune cell infiltration analysis was demonstrated by ESTIMATE and CIBERSORT analysis. Results A total of 174 prognostic IRRlncRNAs were confirmed, and 406 samples were divided into 2 clusters, with cluster 2 having a significantly inferior prognosis. Moreover, cluster 2 exhibited a higher ESTIMATE score, immune infiltration, and PD-L1 expression, with close relationships with the inflammatory response. Further, 12 IRRlncRNAs were identified and applied to construct the risk model and divide BC samples into low-risk and high-risk groups successfully. KM, ROC, and clinical stratification analysis demonstrated that the risk model performed well in predicting prognosis. The risk score was identified as an independently significant indicator, enriched in immune, cell cycle, and apoptosis-related pathways, and correlated with 9 immune cells. Conclusion We developed an inflammatory response-related subtypes and steady prognostic risk model based on 12 IRRlncRNAs, which was valuable for individual prognostic prediction and stratification and outfitted new insight into inflammatory response in BC.
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