Caspase‐7 and Vitamin D Receptor Gene as Key Genes of Hypertension Caused by Pyroptosis in Human DOI Creative Commons

Yuxuan Lou,

Hua Yang, Tingting Wu

et al.

Journal of Clinical Hypertension, Journal Year: 2025, Volume and Issue: 27(4)

Published: April 1, 2025

ABSTRACT This study aims to elucidate the underlying mechanisms of pyroptosis in hypertension through bioinformatics and machine learning approaches. R language was utilized integrate differentially expressed genes (DEGs) between samples healthy control GSE24752 GSE75360 datasets, followed by GO analysis, KEGG enrichment GSEA. Key were screened based on expression levels DEGs using logistic regression, LASSO support vector (SVM). A visualized protein–protein interaction regulatory network constructed, immune cell infiltration analysis performed integrated GEO datasets hypertensive samples. Collect serum from subjects for RT‐qPCR detection key gene expression. total 1005 obtained peripheral blood 13 cases 14 GSEA revealed that function synergistically various biological pathways. regression SVM identified six related (CASP7 (caspase‐7), CYBB, NEK7, NLRP2, RAB5A, VDR (vitamin D receptor)). Immune showed activated B cell, effector memory CD8 T immature MDSC, follicular helper accounted largest proportion cells. results indicated significantly higher relative caspase‐7 vitamin receptor compared controls. These findings suggest CASP7 may offer new research targets diagnosis treatment hypertension, they also provide fresh evidence involvement hypertension.

Language: Английский

The pyroptosis-related gene signature predicts prognosis and indicates immune activity in hepatocellular carcinoma DOI Creative Commons
Min Deng,

Shiquan Sun,

Rongce Zhao

et al.

Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(1)

Published: Feb. 5, 2022

Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors with poor survival. Pyroptosis is a kind programmed cell death that can regulate proliferation, invasion, and metastasis tumor cells. However, expression levels pyroptosis-related genes (PRGs) in HCC their relationship prognosis are still unclear.Our study identified 35 PRGs through bioinformatics analysis were differentially expressed between samples nontumor samples. According to these genes, patients could be divided into two groups, cluster 1 2. The least absolute shrinkage selection operator (LASSO) Cox regression method was performed construct 10-gene signature classified cancer genome atlas (TCGA) database low-risk high-risk groups.The results showed survival rate group significantly higher than (p < 0.001). validation cohort, Gene Expression Omnibus (GEO) risk groups based on median score calculated by TCGA cohort. overall (OS) better = 0.007). Univariate multivariate analyses revealed an independent factor predicting OS patients. Ontology Kyoto Encyclopedia Genes Genomes immune-related rich had reduced immune status.PRGs play significant role immunity have potential capability predict

Language: Английский

Citations

70
Constructing a novel mitochondrial-related gene signature for evaluating the tumor immune microenvironment and predicting survival in stomach adenocarcinoma DOI Creative Commons

Jingjia Chang,

Hao Wu, Jin Wu

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 13, 2023

Abstract Background The incidence and mortality of gastric cancer ranks fifth fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction initiation progression stomach cancer. However, rare prognostic models for mitochondrial-related gene risk been built up in Methods In current study, expression value genes adenocarcinoma (STAD) patients were systematically analyzed to establish a model based on available TCGA GEO databases. tumor microenvironment (TME), immune cell infiltration, mutation burden, drug sensitivity also investigated using R language, GraphPad Prism 8 online Results We established including NOX4, ALDH3A2, FKBP10 MAOA validated its predictive power. This indicated that infiltration high-risk group was significantly different from low-risk group. Besides, score closely related TME signature checkpoint molecules, suggesting immunosuppressive might lead poor prognosis groups. Moreover, TIDE analysis demonstrated combined score, or stromal microsatellite status could more effectively predict benefit immunotherapy STAD with stratifications. Finally, rapamycin, PD-0325901 dasatinib found be effective group, whereas AZD7762, CEP-701 methotrexate predicted Conclusions Our results suggest reliable biomarker personalized treatment patients.

Language: Английский

Citations

48
The role of microRNAs in the gastric cancer tumor microenvironment DOI Creative Commons
Xianzhe Yu,

Yin Zhang,

Fengming Luo

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 20, 2024

Gastric cancer (GC) is one of the deadliest malignant tumors with unknown pathogenesis. Due to its treatment resistance, high recurrence rate, and lack reliable early detection techniques, a majority patients have poor prognosis. Therefore, identifying new tumor biomarkers therapeutic targets essential. This review aims provide fresh insights into enhancing prognosis GC by summarizing processes through which microRNAs (miRNAs) regulate microenvironment (TME) highlighting their critical role in TME. A comprehensive literature was conducted focusing on interactions among cells, extracellular matrix, blood vessels, cancer-associated fibroblasts, immune cells within The noncoding RNAs, known as miRNAs, modulating TME various signaling pathways, cytokines, growth factors, exosomes specifically examined. Tumor formation, metastasis, therapy are significantly influenced miRNAs progression these multiple exosomes. Dysregulation affects cellular such cell proliferation, differentiation, angiogenesis, contributing pathogenesis GC. play crucial regulation TME, influencing patient By understanding mechanisms control potential can be identified improve

Language: Английский

Citations

17
Identification of a disulfidptosis-related genes signature for prognostic implication in lung adenocarcinoma DOI Creative Commons
Jiaqi Huang, Jingyuan Zhang,

Fanqin Zhang

et al.

Computers in Biology and Medicine, Journal Year: 2023, Volume and Issue: 165, P. 107402 - 107402

Published: Aug. 28, 2023

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Additionally, disulfidptosis, a newly discovered type death, has been found to be closely associated with onset and progression tumors. The study first identified genes related disulfidptosis through correlation analysis. These were then screened using univariate cox regression LASSO regression, prognostic model was constructed multivariate regression. A nomogram also created predict prognosis LUAD. validated in three independent data sets: GSE72094, GSE31210, GSE37745. Next, patients grouped based on their median risk score, differentially expressed between two groups analyzed. Enrichment analysis, immune infiltration drug sensitivity evaluation conducted. In this study, we examined 21 developed gene signature that poorer Our datasets showed AUC values greater than 0.5 at 1, 3, 5 years. analysis revealed disulfidptosis-related had multifaceted impact LUAD, particularly relation tumor development, proliferation, metastasis. Patients high-risk group exhibited higher purity lower stromal ESTIMATE Immune score. This analyzed its disease association microenvironment. findings research provide valuable insights into understanding could potentially lead development new treatment strategies.

Language: Английский

Citations

39
Gasdermins: a dual role in pyroptosis and tumor immunity DOI Creative Commons
Jiayi Yang, Jingting Jiang

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 18, 2024

The gasdermin (GSDM) protein family plays a pivotal role in pyroptosis, process critical to the body’s immune response, particularly combatting bacterial infections, impeding tumor invasion, and contributing pathogenesis of various inflammatory diseases. These proteins are adept at activating inflammasome signaling pathways, recruiting effector cells, creating an microenvironment, initiating pyroptosis. This article serves as introduction GSDM protein-mediated pyroptosis providing overview GSDMs’ involvement immunity. Additionally, we explore potential applications GSDMs both innovative established antitumor strategies.

Language: Английский

Citations

8
Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease DOI Creative Commons
Minglin Zhang, Tong Liu, Lijun Luo

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 15, 2025

PANoptosis is one of several modes programmed cell death (PCD) and plays an important role in many inflammatory immune diseases. The bowel disease (IBD) currently unknown. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified, pathway enrichment analyses performed. LASSO regression model construction, a nomogram model, calibration curves, ROC DCA curves used to evaluate the predictive value model. Predicts transcription factors (TFs) small-molecule drugs DE-PRGs analysed. Model immuno-infiltration features IBD include 12 genes: OGT, TLR2, GZMB, TLR4, PPIF, YBX3, CASP5, BCL2L1, CASP6, MEFV, GSDMB BAX. analysis suggested that these related TNF signalling, NF-κB, pyroptosis necroptosis. Machine learning identified three GZMB CASP5. have strong value. Immuno-infiltration revealed infiltration was increased patients with IBD, closely various cells. TFs associated RELA, NFKB1, HIF1A, TP53 SP1. In addition, Connectivity Map (CMap) database top 10 compounds, including buspirone, chloroquine, spectinomycin chlortetracycline. This study indicate good ability for IBD. Moreover, may mediate process through pyroptosis, necroptosis mechanisms. These results present new horizon research treatment

Language: Английский

Citations

1
Pancancer transcriptomic profiling identifies key PANoptosis markers as therapeutic targets for oncology DOI Creative Commons
Raghvendra Mall, Ratnakar R. Bynigeri, Rajendra Karki

et al.

NAR Cancer, Journal Year: 2022, Volume and Issue: 4(4)

Published: Sept. 28, 2022

Abstract Resistance to programmed cell death (PCD) is a hallmark of cancer. While some PCD components are prognostic in cancer, the roles many molecules can be masked by redundancies and crosstalks between pathways, impeding development targeted therapeutics. Recent studies characterizing these have identified PANoptosis, unique innate immune-mediated inflammatory pathway that integrates from other pathways. Here, we designed systematic computational framework determine pancancer clinical significance PANoptosis identify targetable biomarkers. We found high expression genes was detrimental low grade glioma (LGG) kidney renal carcinoma (KIRC). ZBP1, ADAR, CASP2, CASP3, CASP4, CASP8 GSDMD consistently had negative effects on prognosis LGG across multiple survival models, while AIM2, CASP4 TNFRSF10 for KIRC. Conversely, beneficial skin cutaneous melanoma (SKCM), with NLRP1, having positive effects. As therapeutic proof-of-concept, treated cells combination therapy activates ZBP1 showed this treatment induced PANoptosis. Overall, through our framework, validated key immune biomarkers which improve patient outcomes cancers.

Language: Английский

Citations

34
Antitumor Effect of Simvastatin in Combination With DNA Methyltransferase Inhibitor on Gastric Cancer via GSDME-Mediated Pyroptosis DOI Creative Commons
Ying Xia, Yong Jin, Daxiang Cui

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: April 20, 2022

Gasdermin E (GSDME) is one of the executors pyroptosis, a type programmed lytic cell death, which can be triggered by caspase-3 activation upon stimulation. Silenced GSDME expression due to promoter hypermethylation associated with gastric cancer (GC), confirmed in present study bioinformatics analysis and methylation-specific PCR (MSP) test GC lines clinical samples. mouse xenograft models were used investigate pyroptosis-inducing effect common cholesterol-depleting, drug simvastatin (SIM), allied upregulating doxycycline (DOX)- inducible Tet-on system or DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR). Cell viability assessment tumour growth demonstrated that inhibition effects SIM enhanced elevated expression. Morphological examinations assays measuring lactate dehydrogenase (LDH) release caspase-3/GSDME protein cleavage underlined stimulation pyroptosis as an important mechanism. Using short hairpin RNA (shRNA) knockdown GSDME, caspase-3-specific inhibitors, we provided evidence requirement process SIM. We conclude reactivating thereby inducing cell-specific could potential therapeutic strategy against GC.

Language: Английский

Citations

33
Molecular investigation of candidate genes for pyroptosis-induced inflammation in diabetic retinopathy DOI Creative Commons
Nan Wang, Lexi Ding, Die Liu

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: July 25, 2022

Background Diabetic retinopathy is a diabetic microvascular complication. Pyroptosis, as way of inflammatory death, plays an important role in the occurrence and development retinopathy, but its underlying mechanism has not been fully elucidated. The purpose this study to identify potential pyroptosis-related genes by bioinformatics analysis validation model predict microRNAs (miRNAs) long non-coding RNAs (lncRNAs) interacting with them. Subsequently, competing endogenous RNA (ceRNA) regulatory network structured explore their molecular mechanism. Methods We obtained mRNA expression profile dataset GSE60436 from Gene Expression Omnibus (GEO) database collected 51 PubMmed database. differentially expressed were R software, then eight key interest identified correlation analysis, Ontology (GO) enrichment Kyoto Encyclopedia Genes Genomes (KEGG) pathway protein–protein interaction (PPI) analysis. Then, levels these validated quantitative real-time polymerase chain reaction (qRT-PCR) human retinal endothelial cells high glucose incubation, which was used vitro retinopathy. Western blot performed measure protein gasdermin D (GSDMD), dasdermin E (GSDME) cleaved caspase-3 cells. Moreover, aforementioned further confirmed set. Finally, ceRNA structured, miRNAs lncRNAs interacted CASP3, TLR4, GBP2 predicted. Results A total 13 screened six proliferative patients three samples retinas, including one downregulated gene 12 upregulated genes. showed that there among KEGG GO analyses functional roles results mainly related inflammasome complex, interleukin-1 beta production, NOD-like receptor signaling pathway. In addition, hub genes—CASP3, NLRP3, GBP2, CASP1, CASP4, PYCARD, GBP1—were PPI using Cytoscape software. High increased level GSDMD GSDME, critical effectors pyroptosis, vascular Verified qRT-PCR, all consistent chip. Among them, GBP1, GSE179568 dataset. 20 predicted target 22 potentially bind miRNAs. we constructed expected mediate cellular pyroptosis Conclusion Through data GEO software verification qRT-PCR set, successfully involved associated structured. These findings might improve understanding mechanisms

Language: Английский

Citations

32
Pyroptosis-Related Signature Predicts Prognosis and Immunotherapy Efficacy in Muscle-Invasive Bladder Cancer DOI Creative Commons
Qi Zhang, Yezhen Tan,

Jianye Zhang

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 11, 2022

Pyroptosis has profound impacts on tumor cell proliferation, invasion, and metastasis is of great clinical significance for different cancers. However, the role pyroptosis in progression prognosis muscle invasive bladder cancer (MIBC) remains poorly characterized. Here, we collected multicenter MIBC data performed integrated analysis to dissect provide an optimized treatment this disease. Based transcriptomic data, developed a novel prognostic model named pyroptosis-related gene score (PRGScore), which summarizes immunological features, genomic alterations, characteristics associated with phenotype. Samples high PRGScore showed enhancement CD8 + T effector function, antigen processing machinery immune checkpoint better response immunotherapy by programmed death 1 (PD-1) ligand (PD-L1) inhibitors, indicates that valuable signature identification populations sensitive inhibitors. Collectively, our study provides insights into further research targeting its microenvironment (TME) offers opportunity optimize MIBC.

Language: Английский

Citations

29