Pan-cancer genetic analysis of disulfidptosis-related gene set

Cancer Genetics, Journal Year: 2023, Volume and Issue: 278-279, P. 91 - 103

Published: Oct. 10, 2023

Language: Английский

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The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: June 13, 2023

Lung adenocarcinoma (LUAD) is the most common type of lung cancer which accounts for about 40% all cancers. Early detection, risk stratification and treatment are important improving outcomes LUAD. Recent studies have found that abnormal accumulation cystine other disulfide occurs in cell under glucose starvation, induces stress increases content bond actin cytoskeleton, resulting death, defined as disulfidptosis. Because study disulfidptosis its infancy, role disease progression still unclear. In this study, we detected expression mutation genes LUAD using a public database. Clustering analysis based on gene was performed differential subtype were analyzed. 7 used to construct prognostic model, causes differences investigated by immune-infiltration analysis, immune checkpoint drug sensitivity analysis. qPCR verify key line (A549) normal bronchial epithelial (BEAS-2B). Since G6PD had highest factor cancer, further verified protein cells western blot, confirmed through colony formation experiment interference with able significantly inhibit proliferation ability cells. Our results provide evidence new ideas individualized precision therapy

Language: Английский

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Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 11, 2023

Regulatory T cells (Treg), as members of CD4+ cells, have garnered extensive attention in the research tumor progression. Treg function inhibiting immune effector preventing tissue damage, and suppressing inflammation. Under stimulation inflammatory microenvironment (IM), reprogramming enhances their suppression responses, ultimately promoting escape or Reducing number IM lowering activity while reprogramming, can help promote body's anti-tumor responses. This review introduces a mechanism IM; discusses regulation on The control response to immunotherapy are analyzed countermeasures proposed. work will provide foundation for downregulating immunosuppressive role environment future immunotherapy.

Language: Английский

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Identification of disulfidptosis related subtypes, characterization of tumor microenvironment infiltration, and development of DRG prognostic prediction model in RCC, in which MSH3 is a key gene during disulfidptosis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 23, 2023

Disulfidptosis is a newly discovered mode of cell death induced by disulfide stress. However, the prognostic value disulfidptosis-related genes (DRGs) in renal carcinoma (RCC) remains to be further elucidated. In this study, consistent cluster analysis was used classify 571 RCC samples into three DRG-related subtypes based on changes DRGs expression. Through univariate regression and LASSO-Cox differentially expressed (DEGs) among subtypes, we constructed validated DRG risk score predict prognosis patients with RCC, while also identifying gene subtypes. Analysis score, clinical characteristics, tumor microenvironment (TME), somatic mutations, immunotherapy sensitivity revealed significant correlations between them. A series studies have shown that MSH3 can potential biomarker its low expression associated poor RCC. Last but not least, overexpression promotes two lines under glucose starvation conditions, indicating key process disulfidptosis. summary, identify mechanism progression through -related remodeling. addition, study has successfully established new prediction model . They may biomarkers for patients, provide insights treatment inspire methods diagnosis patients.

Language: Английский

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Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Oct. 17, 2023

Background: Colon cancer, a prevalent and deadly malignancy worldwide, ranks as the third leading cause of cancer-related mortality. Disulfidptosis stress triggers unique form programmed cell death known disulfidoptosis, characterized by excessive intracellular cystine accumulation. This study aimed to establish reliable bioindicators based on long non-coding RNAs (LncRNAs) associated with disulfidptosis-induced death, providing novel insights into immunotherapeutic response prognostic assessment in patients colon adenocarcinoma (COAD). Methods: Univariate Cox proportional hazard analysis Lasso regression were performed identify differentially expressed genes strongly prognosis. Subsequently, multifactorial model for risk was developed using multiple regression. Furthermore, we conducted comprehensive evaluations characteristics disulfidptosis response-related LncRNAs, considering clinicopathological features, tumor microenvironment, chemotherapy sensitivity. The expression levels prognosis-related COAD validated quantitative real-time fluorescence PCR (qRT-PCR). Additionally, role ZEB1-SA1 cancer investigated through CCK8 assays, wound healing experiment transwell experiments. Results: LncRNAs identified robust predictors Multifactorial revealed that score derived from these served an independent factor COAD. Patients low-risk group exhibited superior overall survival (OS) compared those high-risk group. Accordingly, our Nomogram prediction model, integrating clinical scores, demonstrated excellent efficacy. In vitro experiments promoted proliferation migration cells. Conclusion: Leveraging medical big data artificial intelligence, constructed TCGA-COAD cohort, enabling accurate patients. implementation this practice can facilitate precise classification patients, identification specific subgroups more likely respond favorably immunotherapy chemotherapy, inform development personalized treatment strategies scientific evidence.

Language: Английский

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The expression and prognostic value of disulfidptosis progress in lung adenocarcinoma

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 7, 2023

Disulfidptosis is a new cell death model caused by accumulating intracellular disulfides bonding to actin cytoskeleton proteins. This study aimed investigate the expression and prognostic value of disulfidptosis-related genes (DRGs) in lung adenocarcinoma (LUAD). The data profiles scRNA-seq were collected from TCGA GEO databases. different expressions DRGs between normal LUAD tissues compared. LASSO analysis multivariate Cox regression utilized develop for prognosis evaluation LUAD. model's predictive accuracy was evaluated with area under receiver operating characteristic curve (AUC) C-index. Survival analysis, univariate used assessing model. ScRNA-seq analyzed "Seurat" "Monocle 2" packages. There significant differences 22 tumor tissues. A five (ACTB, FLNB, NCKAP1, SLC3A2, SLC7A11) constructed. AUC C-index significantly higher than that based on clinical parameters. demonstrated risk score an independent predictor. In study, we identified 14 clusters 11 types. Clusters 2, 8, 13 annotated into Epithelial cells. SLC7A11 NCKAP1 ACTB expressed most abundantly cells, Endothelial Naive CD4 T, respectively. We explored constructed model, which stable reliable predicting prognosis.

Language: Английский

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Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: April 29, 2024

Abstract Cell death is an important part of the life cycle, serving as a foundation for both orderly development and maintenance physiological equilibrium within organisms. This process fundamental, it eliminates senescent, impaired, or aberrant cells while also promoting tissue regeneration immunological responses. A novel paradigm programmed cell death, known disulfidptosis, has recently emerged in scientific circle. Disulfidptosis defined accumulation cystine by cancer with high expression solute carrier family 7 member 11 (SLC7A11) during glucose starvation. causes extensive disulfide linkages between F-actins, resulting their contraction subsequent detachment from cellular membrane, triggering death. The RAC1-WRC axis involved this phenomenon. sparked growing interest due to its potential applications variety pathologies, particularly oncology, neurodegenerative disorders, metabolic anomalies. Nonetheless, complexities regulatory pathways remain elusive, precise molecular targets have yet be definitively identified. manuscript aims meticulously dissect historical evolution, underpinnings, frameworks, implications disulfidptosis various disease contexts, illuminating promise groundbreaking therapeutic pathway target.

Language: Английский

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Identification of disulfidptosis-related genes and subgroups in Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Aug. 4, 2023

Background Alzheimer’s disease (AD), a common neurological disorder, has no effective treatment due to its complex pathogenesis. Disulfidptosis, newly discovered type of cell death, seems be closely related the occurrence various diseases. In this study, through bioinformatics analysis, expression and function disulfidptosis-related genes (DRGs) in were explored. Methods Differential analysis was performed on gene matrix AD, intersection differentially expressed AD obtained. Hub further screened using multiple machine learning methods, predictive model constructed. Finally, 97 samples divided into two subgroups based hub genes. Results total 22 overlapping identified, 7 obtained learning, including MYH9, IQGAP1, ACTN4, DSTN, ACTB, MYL6, GYS1. Furthermore, diagnostic capability validated external datasets clinical samples. Based these genes, constructed, with large area under curve (AUC = 0.8847), AUCs validation also higher than 0.7, indicating high accuracy model. Using unsupervised clustering Cluster1 ( n 24) Cluster2 73), most at levels Cluster2. Immune infiltration revealed that had level immune scores. Conclusion A close association between disulfidptosis established assess risk subtype patients. This study provides new perspectives for exploring biomarkers potential therapeutic targets disease.

Language: Английский

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An integrative multi-omics analysis based on disulfidptosis-related prognostic signature and distinct subtypes of clear cell renal cell carcinoma

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: June 23, 2023

The association between clear cell renal carcinoma (ccRCC) and disulfidoptosis remains to be thoroughly investigated.We conducted multiple bioinformatics analyses, including prognostic analysis cluster analysis, using R software. Additionally, we utilized Quantitative Real-time PCR measure RNA levels of specific genes. proliferation ccRCC was assessed through CCK8 colony formation assays, while the invasion migration cells were evaluated transwell assay.In this study, utilizing data from cohorts, identified molecules that contribute disulfidoptosis. We a comprehensive investigation into immunological roles these molecules. Among disulfidoptosis-related metabolism genes (DMGs), LRPPRC, OXSM, GYS1, SLC7A11 exhibited significant correlations with patient prognosis. Based on our signature, patients in different groups displayed varying immune infiltration mutation profiles. Furthermore, classified two clusters functional pathways play important occurrence development ccRCC. Given its critical role disulfidoptosis, further SLC7A11. Our results demonstrated high expression malignant phenotype.These findings enhanced understanding underlying function DMGs

Language: Английский

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Identification of peripheral blood immune infiltration signatures and construction of monocyte-associated signatures in ovarian cancer and Alzheimer's disease using single-cell sequencing

Heliyon, Journal Year: 2023, Volume and Issue: 9(7), P. e17454 - e17454

Published: June 28, 2023

Ovarian cancer (OC) is a common tumor of the female reproductive system, while Alzheimer's disease (AD) prevalent neurodegenerative that primarily affects cognitive function in elderly. Monocytes are immune cells blood can enter tissues and transform into macrophages, thus participating inflammatory responses. Overall, monocytes may play an important role ovarian cancer.The CIBERSORT algorithm results indicate potential crucial monocytes/macrophages OC AD. To identify monocyte marker genes, single-cell RNA-seq data peripheral mononuclear (PBMCs) from AD patients were analyzed. Enrichment analysis various cell subpopulations was performed using "irGSEA" R package. The estimation cycle conducted with "tricycle" package, intercellular communication networks analyzed "CellChat". For 134 monocyte-associated genes (MRGs), bulk two diseased obtained. Cox regression employed to develop risk models, categorizing high-risk (HR) low-risk (LR) groups. model's accuracy validated external GEO cohort. different groups evaluated terms infiltration, mutational status, signaling pathways, checkpoint expression, immunotherapy. characteristic MRGs AD, machine learning algorithms, namely random forest support vector (SVM), utilized.Based on analysis, model consisting seven developed OC, indicating better prognosis for LR group. group had higher mutation burden, infiltration abundance, expression. TIDE IMvigor210 cohort showed more likely benefit Finally, ZFP36L1 AP1S2 identified as affecting progression.The profile containing this study help further guide clinical management targeted therapy OC. serve biomarkers new therapeutic targets

Language: Английский

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