Dataset Information

Prognostic Inflammasome-Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan-Cancer Landscape.

ABSTRACT: Objective:To investigate the expression patterns and prognostic characteristics of inflammasome-related genes (IRGs) across cancer types and develop a robust biomarker for the prognosis of KIRC. Methods:The differentially expressed IRGs and prognostic genes among 10 cancers were analyzed based on The Cancer Genome Atlas (TCGA) dataset. Subsequently, an IRGs risk signature was developed in KIRC. Its prognostic accuracy was evaluated by receiver operating characteristic (ROC) analysis. The independent predictive capacity was identified by stratification survival and multivariate Cox analyses. The gene ontology (GO) analysis and principal component analysis (PCA) were performed to explore biological functions of the IRGs signature in KIRC. Results:The expression patterns and prognostic association of IRGs varied from different cancers, while KIRC showed the most abundant survival-related dysregulated IRGs. The IRG signature for KIRC was able to independently predict survival, and the signature genes were mainly involved inimmune-related processes. Conclusions:The pan-cancer analysis provided a comprehensive landscape of IRGs across cancer types and identified a strong association between IRGs and the prognosis of KIRC. Further IRGs signature represented a reliable prognostic predictor for KIRC and verified the prognostic value of inflammasomes in KIRC, contributing to our understanding of therapies targeting inflammasomes for human cancers.

SUBMITTER: Zheng T

PROVIDER: S-EPMC7157792 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prognostic Inflammasome-Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan-Cancer Landscape.

Zheng Tianyu T Wang Xindong X Yue Peipei P Han Tongtong T Hu Yue Y Wang Biyao B Zhao Baohong B Zhang Xinwen X Yan Xu X

Evidence-based complementary and alternative medicine : eCAM 20200403

<h4>Objective</h4>To investigate the expression patterns and prognostic characteristics of inflammasome-related genes (IRGs) across cancer types and develop a robust biomarker for the prognosis of KIRC.<h4>Methods</h4>The differentially expressed IRGs and prognostic genes among 10 cancers were analyzed based on The Cancer Genome Atlas (TCGA) dataset. Subsequently, an IRGs risk signature was developed in KIRC. Its prognostic accuracy was evaluated by receiver operating characteristic (ROC) analys ...[more]

PMID: 32328125

Similar Datasets

Project description:BackgroundKidney renal clear cell carcinoma (KIRC) lacks effective prognostic biomarkers and the role and mechanism of N6-methyladenosine (m6A) modification of long noncoding RNAs (lncRNAs) in KIRC remain unclear.MethodsWe extracted standard mRNA-sequencing and clinical data from the TCGA database. The prognostic risk model was obtained by Lasso regression and Cox regression. We randomly divided the samples into training and test sets, each taking half of the cases. Based on Lasso regression and Cox regression for training set, the prognostic risk signature was constructed; risk scores were calculated with the R package "glmnet." Based on the median value of the prognostic risk score, risk scores were calculated for each patient and we divided all KIRC samples into high-risk and low-risk groups. Then, high- and low-risk subtypes were established and their prognosis, clinical features, and immune infiltration microenvironment were evaluated in test set and the entire sampled data set. The reliability of the prognostic model was confirmed by receiver operating characteristic curve analysis.ResultsWe found 28 prognostic m6A-related lncRNAs and established a m6A-related lncRNAs prognostic signature. Risk score=AC015813.1∗(0.0086)+EMX2OS∗(-0.0101)+LINC00173∗(0.0309)+PWAR5∗(-0.0146)+SNHG1∗(0.0043). The signature showed a better predictive ability than other clinical indicators, including tumor node metastasis classification (TNM), histological, and pathological stages. In the high-risk group, M0 macrophages, CD8+ T cells, and regulatory T cells had significantly higher scores. Contrarily, in the low-risk group, activated dendritic cells, M1 macrophages, mast resting cells, and monocytes had significantly higher scores. In the high-risk group, LSECtin was overexpressed. In the low-risk group, PD-L1 was overexpressed. Moreover, high-risk patients may benefit more from AZ628.ConclusionsIn conclusion, prognosis prediction of patients with KIRC and new insights for immunotherapy are provided by the m6A-related lncRNA prognostic signature.

Project description:BackgroundMETTL14, as one of N6-methyladenosine (m6A) related genes, has been found to be associated with promoting tumorigenesis in different types of cancers. This study was aimed to investigate the prognostic value of METTL14 in clear cell renal cell carcinoma (ccRCC).MethodsWe collected ccRCC patients' clinicopathological parameters information and 13 m6A related genes expression from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to investigate whether METTL14 could serve as an independent factor correlated with overall survival (OS). Gene Set Enrichment Analysis (GSEA) was carried out to identify METTL14-related signaling pathways. Moreover, a risk score (RS) was calculated to predict the prognosis of ccRCC. Quantitative real-time PCR (qRT-PCR) was also utilized to verify the expression of METTL14 in clinical specimens.ResultsDifferently expressed m6A related genes were identified between ccRCC tissues and normal tissues. Therein, METTL14 was lowly expressed in ccRCC tissues and verified by qRT-PCR (all p < 0.01). Survival analysis indicated that high expression of METTL14 was associated with better OS (p = 1e-05). GSEA results revealed that high METTL14 expression was enriched in ERBB pathway, MAPK pathway, mTOR pathway, TGF-β pathway and Wnt pathway. Moreover, METTL14 was proved to be an independent prognostic factor by means of univariate and multivariate Cox regression analyses. Nomogram integrating both the METTL14 expression and clinicopathologic variables was also established to provide clinicians with a quantitative approach for predicting survival probabilities of ccRCC. Furthermore, a METTL14-based riskscore (RS) was developed with significant OS (p = 6.661e-16) and increased AUC of 0.856. Besides, significant correlated genes with METTL14 were also provided.ConclusionsOur results indicated that METTL14 could serve as a favorable prognostic factor for ccRCC. Moreover, this study also provided a prognostic signature to predict prognosis of ccRCC and identified METTL14-related signaling pathways.

Project description:Background: Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). Anoikis plays an essential function in tumourigenesis, whereas the role of anoikis in ccRCC remains unclear. Methods: Anoikis-related genes (ARGs) were collected from the MSigDB database. According to univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO) algorithm was utilized to select the ARGs associated with the overall rate (OS). Multivariate Cox regression analysis was conducted to identify 5 prognostic ARGs, and a risk model was established. The Kaplan-Meier survival analysis was used to evaluate the OS rate of ccRCC patients. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Gene set enrichment analysis (GSVA) were utilized to investigate the molecular mechanism of patients in the low- and high-risk group. ESTIMATE, CIBERSOT, and single sample gene set enrichment analysis (ssGSEA) algorithms were conducted to estimate the immune infiltration landscape. Consensus clustering analysis was performed to divide the patients into different subgroups. Results: A fresh risk model was constructed based on the 5 prognostic ARGs (CHEK2, PDK4, ZNF304, SNAI2, SRC). The Kaplan-Meier survival analysis indicated that the OS rate of patients with a low-risk score was significantly higher than those with a high-risk score. Consensus clustering analysis successfully clustered the patients into two subgroups, with a remarkable difference in immune infiltration landscape and prognosis. The ESTIMATE, CIBERSORT, and ssGSEA results illustrated a significant gap in immune infiltration landscape of patients in the low- and high-risk group. Enrichment analysis and GSVA revealed that immune-related signaling pathways might mediate the role of ARGs in ccRCC. The nomogram results illustrated that the ARGs prognostic signature was an independent prognostic predictor that distinguished it from other clinical characteristics. TIDE score showed a promising immunotherapy response of ccRCC patients in different risk subgroups and cluster subgroups. Conclusion: Our study revealed that ARGs play a carcinogenic role in ccRCC. Additionally, we firstly integrated multiple ARGs to establish a risk-predictive model. This study highlights that ARGs could be implemented as a stratification factor for individualized and precise treatment in ccRCC patients.

Project description:BackgroundRecent studies have demonstrated that long non-coding RNAs (lncRNAs) are involved in regulating tumor cell ferroptosis. However, prognostic signatures based on ferroptosis-related lncRNAs (FRLs) and their relationship to the immune microenvironment have not been comprehensively explored in clear cell renal cell carcinoma (ccRCC).MethodsIn the present study, the expression profiles of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database; 459 patient specimens and 69 adjacent normal tissues were randomly separated into training or validation cohorts at a 7:3 ratio. We identified 7 FRLs that constitute a prognostic signature according to the differential analysis, correlation analysis, univariate regression, and least absolute shrinkage and selection operator (LASSO) Cox analysis. To identify the independence of risk score as a prognostic factor, univariate and multivariate regression analyses were also performed. Furthermore, CIBERSORT was conducted to analyze the immune infiltration of patients in the high-risk and low-risk groups. Subsequently, the differential expression of immune checkpoint and m6A genes was analyzed in the two risk groups.ResultsA 7-FRLs prognostic signature of ccRCC was developed to distinguish patients into high-risk and low-risk groups with significant survival differences. This signature has great prognostic performance, with the area under the curve (AUC) for 1, 3, and 5 years of 0.713, 0.700, 0.726 in the training set and 0.727, 0.667, and 0.736 in the testing set, respectively. Moreover, this signature was significantly associated with immune infiltration. Correlation analysis showed that risk score was positively correlated with regulatory T cells (Tregs), activated CD4 memory T cells, CD8 T cells and follicular helper T cells, whereas it was inversely correlated with monocytes and M2 macrophages. In addition, the expression of fourteen immune checkpoint genes and nine m6A-related genes varied significantly between the two risk groups.ConclusionWe established a novel FRLs-based prognostic signature for patients with ccRCC, containing seven lncRNAs with precise predictive performance. The FRLs prognostic signature may play a significant role in antitumor immunity and provide a promising idea for individualized targeted therapy for patients with ccRCC.

Project description:Introduction: Kidney renal clear cell carcinoma (KIRC), a kind of malignant disease, is a severe threat to public health. Tracking the information of tumor progression and conducting a related dynamic prognosis model are necessary for KIRC. It is crucial to identify hypoxia-immune-related genes and construct a prognostic model due to immune interaction and the influence of hypoxia in the prognosis of patients with KIRC. Methods: The hypoxia and immune status of KIRC patients were identified by utilizing t-SNE and ImmuCellAI for gene expression data. COX and Lasso regression were used to identify some hypoxia-immune-related signature genes and further construct a prognostic risk model based on these genes. Internal and external validations were also conducted to construct a prognostic model. Finally, some potentially effective drugs were screened by the CMap dataset. Results: We found that high-hypoxia and low-immune status tend to induce poor overall survival (OS). Six genes, including PLAUR, UCN, PABPC1L, SLC16A12, NFE2L3, and KCNAB1, were identified and involved in our hypoxia-immune-related prognostic risk model. Internal verification showed that the area under the curve (AUC) for the constructed models for 1-, 3-, 4-, and 5-year OS were 0.768, 0.754, 0.775, and 0.792, respectively. For the external verification, the AUC for 1-, 3-, 4-, and 5-year OS were 0.768, 0.739, 0.763, and 0.643 respectively. Furthermore, the decision curve analysis findings demonstrated excellent clinical effectiveness. Finally, we found that four drugs (including vorinostat, fludroxycortide, oxolinic acid, and flutamide) might be effective and efficient in alleviating or reversing the status of severe hypoxia and poor infiltration of immune cells. Conclusion: Our constructed prognostic model, based on hypoxia-immune-related genes, has excellent effectiveness and clinical application value. Moreover, some small-molecule drugs are screened to alleviate severe hypoxia and poor infiltration of immune cells.

Dataset Information

Prognostic Inflammasome-Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan-Cancer Landscape.

Publications

Prognostic Inflammasome-Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan-Cancer Landscape.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets