Identification of the pyroptosis‑related prognostic gene signature and the associated regulation axis in lung adenocarcinoma

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: June 25, 2021

Abstract Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. Pyroptosis could regulate tumour cell proliferation, invasion, metastasis, thereby affecting prognosis of cancer patients. However, role pyroptosis-related genes (PRGs) in LUAD unclear. In our study, comprehensive bioinformatics analysis was performed to construct prognostic gene model ceRNA network. The correlations between PRGs tumour-immune infiltration, mutation burden, microsatellite instability were evaluated using Pearson’s correlation analysis. A total 23 upregulated or downregulated LUAD. genetic variation landscape PRG also summarised. Functional enrichment revealed that these 33 mainly involved pyroptosis, NOD-like receptor signalling pathway, Toll-like pathway. Prognosis indicated survival rate patients with low expression NLRP7, NLRP1, NLRP2, NOD1 high CASP6 expression. constructed above five predict overall medium-to-high accuracy. Significant observed immune-cell instability. network identify lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis conclusion, we identified signature containing (NLRP7, NOD1, CASP6) for Our results axis, which may play an important progression Further study needs be conducted verify this result.

Language: Английский

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Identification of pyroptosis-related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in colorectal cancer

OncoImmunology, Journal Year: 2021, Volume and Issue: 10(1)

Published: Jan. 1, 2021

Pyroptosis is a newly discovered programmed cell death that associated with tumor progression, prognosis, and treatment response. However, the potential roles of pyroptosis-related genes (PRGs) in microenvironment (TME) remain unclear. We described alterations PRGs 1109 colorectal cancer (CRC) samples from genetic transcriptional fields evaluated their expression patterns four independent datasets. identified two distinct molecular subtypes found multi-layer PRG were correlated patient clinicopathological features, TME cell-infiltrating characteristics. Then, PRG_score for predicting recurrence-free survival (RFS) was constructed its predictive capability CRC patients validated. Consequently, we highly accurate nomogram improving clinical applicability PRG_score. A low PRG_score, characterized by increased microsatellite instability-high (MSI-H), mutation burden, immunity activation, indicated favorable odds RFS. Moreover, significantly stem (CSC) index chemotherapeutic drug sensitivity. Our comprehensive analysis demonstrated tumor-immune-stromal microenvironment, prognosis. These findings may improve our understanding pave new path assessment prognosis development more effective immunotherapy strategies.

Language: Английский

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Efficient plasma metabolic fingerprinting as a novel tool for diagnosis and prognosis of gastric cancer: a large-scale, multicentre study

Gut, Journal Year: 2023, Volume and Issue: 72(11), P. 2051 - 2067

Published: July 17, 2023

Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead high-performance blood tests towards GC diagnosis prognosis. We attempted develop diagnostic prognostic models for based on plasma metabolic information.We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort 264 prospective cohort. Discovery verification phases were through machine learning Cox regression fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, developed model was validated both NPELDI-MS ultra-performance liquid chromatography-MS (UPLC-MS).We demonstrated high throughput, desirable reproducibility limited centre-specific effects PMFs NPELDI-MS. In cohort, we achieved performance with areas under curves (AUCs) 0.862-0.988 discovery (n=1157 5 centres) independent external dataset (n=787 another 2 centres), different PMFs, including neural network, ridge regression, lasso support vector random forest. Further, panel consisting 21 metabolites constructed identified AUCs 0.921-0.971 0.907-0.940 dataset, respectively. (n=264 centre), UPLC-MS applied detect validate panel, 0.855-0.918 0.856-0.916, Moreover, prognosis scoring system which can effectively predict survival patients.We GC, also contribute advanced analysis diseases, but not GC.

Language: Английский

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Regulatory T cells subgroups in the tumor microenvironment cannot be overlooked: Their involvement in prognosis and treatment strategy in melanoma

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(10), P. 4512 - 4530

Published: March 26, 2024

Abstract Background Melanoma, the most lethal form of skin cancer, presents substantial challenges despite effective surgical interventions for in situ lesions. Regulatory T cells (Tregs) wield a pivotal immunomodulatory influence within tumor microenvironment, yet their impact on melanoma prognosis and direct molecular interactions with remain elusive. This investigation employs single‐cell analysis to unveil intricate nature Tregs human melanoma. Methods Single‐cell RNA bulk sequencing data, alongside clinical information, were obtained from public repositories. Initially, GO GSEA analyses employed delineate functional disparities among distinct cell subsets. Pseudotime cell–cell interconnection conducted, followed by an endeavor construct prognostic model grounded Treg‐associated risk scores. model's efficacy was demonstrated via PCA K‐M analyses, multivariate Cox regression affirming its independent value patients. Furthermore, immune infiltration analysis, checkpoint gene expression scrutiny, drug sensitivity assessments performed ascertain relevance this model. Results Following batch effect correction, 80 025 partitioned into 31 clusters, encompassing B cells, plasma endothelial fibroblasts, monocytes, macrophages, T_NK cells. Within these, 4240 CD4+ subclassified seven types. Functional underscored function elucidating Treg subpopulations. Notably, ITGB2 signaling pathway emerged as plausible nexus linking Our signature exhibited robust predictive capacities potential implications evaluating immunotherapy response. Conclusion exert critical role suppression revealing molecular‐level association innovative Treg‐centered introduces promising marker melanoma, holding future assessments.

Language: Английский

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Identification and Validation of Pyroptosis-Related Gene Signature to Predict Prognosis and Reveal Immune Infiltration in Hepatocellular Carcinoma

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Nov. 8, 2021

Background: Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and accounts for the fourth common cause of cancer-related deaths. Recently, pyroptosis has been revealed to be involved in progression multiple cancers. However, role HCC remains elusive. Methods: The clinical information RNA-seq data patients were collected from TCGA-LIHC datasets, differential pyroptosis-related genes (PRG) firstly explored. univariate Cox regression consensus clustering applied recognize subtypes. prognostic PRGs then submitted LASSO analysis build model TCGA training cohort. We further evaluated predictive test cohort ICGC validation (LIRI-JP). accuracy prediction was validated using Kaplan-Meier (K-M) receiver operating characteristic (ROC) analyses. single-sample gene set enrichment (ssGSEA) used determine immune cell infiltrations related pathways. Finally, expression qRT-PCR vivo vitro. Results: identified total 26 PRGs, among which three comprising GSDME, GPX4, SCAF11 subsequently chosen constructing model. This significantly distinguished with different survival years training, test, cohorts. risk score this confirmed as an independent factor. A nomogram generated indicating each patient. ssGSEA demonstrated several tumor-infiltrating cells remarkably associated scores. results also showed apparent dysregulation HCC. drug sensitivity analyzed, that Lenvatinib might impact via targeting human Huh7 cells. Conclusion: PRG signature comprised can serve factor patients, would provide evidence more functional studies.

Language: Английский

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The pyroptosis-related gene signature predicts prognosis and indicates immune activity in hepatocellular carcinoma

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

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Pyroptosis-related lncRNAs are potential biomarkers for predicting prognoses and immune responses in patients with UCEC

Molecular Therapy — Nucleic Acids, Journal Year: 2022, Volume and Issue: 27, P. 1036 - 1055

Published: Jan. 25, 2022

Uterine corpus endometrial carcinoma (UCEC) is a malignant disease globally, and there no unified prognostic signature at present. In our study, two clusters were identified. Cluster 1 showed better prognosis higher infiltration level, such as tumor microenvironment (TME), mutation burden (TMB), immune checkpoint genes expression. Gene set enrichment analysis (GSEA) indicated that some tumor-related pathways immune-associated exposed. What more, six pyroptosis-related long noncoding RNAs (lncRNAs) (PRLs) applied to establish through multiple Cox regression analysis. both training testing sets, patients with risk score had poorer survival than low risk. The area under the curve (AUC) of receiver operating characteristic (ROC) curves performed probability was in people lower score. Mechanism revealed high correlated reduced T cells exhaustion, matching definition an "immune-desert" phenotype. Patients characterized by gene expression TMB have sensitive response immunotherapy chemotherapy compared has accurate prediction ability UCEC promising therapeutic target improve effect immunotherapy.

Language: Английский

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Ferroptosis, necroptosis, and pyroptosis in the occurrence and development of ovarian cancer

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

Published: July 25, 2022

Ovarian cancer (OC) is one of the most common malignancies that causes death in women and a heterogeneous disease with complex molecular genetic changes. Because relatively high recurrence rate OC, it crucial to understand associated mechanisms drug resistance discover potential target for rational targeted therapy. Cell genetically determined process. Active orderly cell prevalent during development living organisms plays critical role regulating life homeostasis. Ferroptosis, novel type discovered recent years, distinct from apoptosis necrosis mainly caused by imbalance between production degradation intracellular lipid reactive oxygen species triggered increased iron content. Necroptosis regulated non-cysteine protease–dependent programmed necrosis, morphologically exhibiting same features as occurring via unique mechanism different apoptotic signaling pathway. Pyroptosis form characterized formation membrane pores subsequent lysis well release pro-inflammatory contents mediated abscisin family. Studies have shown ferroptosis, necroptosis, pyroptosis are involved progression variety diseases, including tumors. In this review, we summarized advances occurrence, development, therapeutic OC.

Language: Английский

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Novel necroptosis-related gene signature for predicting the prognosis of pancreatic adenocarcinoma

Aging, Journal Year: 2022, Volume and Issue: 14(2), P. 869 - 891

Published: Jan. 24, 2022

Pancreatic adenocarcinoma (PAAD) is a deadly digestive system tumor with poor prognosis. Recently, necroptosis has been considered as type of inflammatory programmed cell death. However, the expression necroptosis-related genes (NRGs) in PAAD and their associations prognosis remain unclear. NRGs’ prediction potential samples from The TCGA GEO datasets was investigated. model constructed using Lasso regression. Co-expression analysis showed that gene closely related to necroptosis. NRGs were shown be somewhat overexpressed high-risk people even when no other clinical symptoms present, indicating they may utilized predict GSEA immunological tumor-related pathways group. Based on findings, immune function m6A differ significantly between low-risk groups. MET, AM25C, MROH9, MYEOV, FAM111B, Y6D, PPP2R3A might oncology process for patients. Moreover, CASKIN2, TLE2, USP20, SPRN, ARSG, MIR106B, MIR98 associated patients PAAD. relationship function, checkpoints, therapeutic targets should further studied.

Language: Английский

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A novel Alzheimer’s disease prognostic signature: identification and analysis of glutamine metabolism genes in immunogenicity and immunotherapy efficacy

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: April 27, 2023

Abstract Alzheimer’s disease (AD) is characterized as a distinct onset and progression of cognitive functional decline associated with age, well specific neuropathology. It has been discovered that glutamine (Gln) metabolism plays crucial role in cancer. However, full investigation its still missing. This study intended to find confirm potential Gln-related genes AD using bioinformatics analysis. The discovery GlnMgs was made possible by the intersection WGCNA test 26 Gln-metabolism (GlnMgs). GlnMgs’ putative biological functions pathways were identified GSVA. LASSO method then used identify hub diagnostic efficiency four identifying AD. association between clinical characteristics also studied. Finally, GSE63060 utilized levels expression GlnMgs. Four (ATP5H, NDUFAB1, PFN2, SPHKAP). For function analysis, cell fate specification, atrioventricular canal development, neuron specification emphasized. ability differentiating exhibited good value. are linked They shed light on new biomarkers for tracking progression.

Language: Английский

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