Identification of cancer stem cell-related genes through single cells and machine learning for predicting prostate cancer prognosis and immunotherapy

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

Published: Aug. 29, 2024

Background Cancer stem cells (CSCs) are a subset of within tumors that possess the unique ability to self-renew and give rise diverse tumor cells. These crucial in driving metastasis, recurrence, resistance treatment. The objective this study was pinpoint essential regulatory genes associated with CSCs prostate adenocarcinoma (PRAD) assess their potential significance diagnosis, prognosis, immunotherapy patients PRAD. Method utilized single-cell analysis techniques identify cell-related evaluate relation patient prognosis PRAD through cluster analysis. By utilizing datasets employing various machine learning methods for clustering, diagnostic models were developed validated. random forest algorithm pinpointed HSPE1 as most prognostic gene among genes. Furthermore, delved into association between immune infiltration, employed molecular docking investigate relationship its compounds. Immunofluorescence staining 60 tissue samples confirmed expression correlation Result This identified 15 analysis, highlighting importance diagnosing, prognosticating, potentially treating patients. specifically linked response immunotherapy, experimental data supporting upregulation poorer prognosis. Conclusion Overall, our findings underscore significant role unveil novel target related cell.

Language: Английский

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The gut microbiome, immune modulation, and cognitive decline: insights on the gut-brain axis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

The gut microbiome has emerged as a pivotal area of research due to its significant influence on the immune system and cognitive functions. Cognitive disorders, including dementia Parkinson’s disease, represent substantial global health challenges. This review explores relationship between microbiota, modulation, decline, with particular focus gut-brain axis. Research indicates that bacteria produce metabolites, short-chain fatty acids (SCFAs), which affect mucosal immunity, antigen presentation, responses, thereby influencing A noteworthy correlation been identified imbalances in impairments, suggesting novel pathways for treatment disorders. Additionally, factors such diet, environment, pharmaceuticals play role shaping composition microbiome, subsequently impacting both health. article aims clarify complex interactions among regulation, evaluating their potential therapeutic targets. goal is promote microbiome-based treatments lay groundwork future this field.

Language: Английский

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Overcoming immune evasion with innovative multi-target approaches for glioblastoma

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

Glioblastoma (GBM) cells leverage complex endogenous and environmental regulatory mechanisms to drive proliferation, invasion, metastasis. Tumor immune evasion, facilitated by a multifactorial network, poses significant challenge effective therapy, as evidenced the limited clinical benefits of monotherapies, highlighting adaptive nature evasion. This review explores glioblastoma’s evasion mechanisms, role ICIs in tumor microenvironment, recent advancements, offering theoretical insights directions for monotherapy combination therapy glioblastoma management.

Language: Английский

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Pan-cancer analysis of Arp2/3 complex subunits: focusing on ARPC1A’s role and validating the ARPC1A/c-Myc axis in non-small cell lung cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

The Arp2/3 complex is a key regulator of tumor metastasis, and targeting its subunits offers potential for anti-metastatic therapy. However, the expression profiles, prognostic relevance, diagnostic value across cancers remain poorly understood. This study aims to investigate clinical relevance subunits, particularly ARPC1A, in pan-cancer, further analyze biological mechanisms as well association with immune infiltration chemotherapy drug sensitivity. To explore differential their cancers, we analyzed data from TCGA GTEx databases. relationship between ARPC1A infiltration, interactions functional proteins, was examined using TCPA TIMER2.0 Gene Set Enrichment Analysis (GSEA) performed identify ARPC1A-associated signaling pathways. Chemotherapy sensitivity correlated assessed CellMiner, GDSC, CTRP effect on c-Myc validated by quantitative PCR (qPCR) Western blot. Finally, role non-small cell lung cancer (NSCLC) cells CCK-8, EdU incorporation, colony formation, Transwell assays. are frequently overexpressed majority correlating poor outcomes demonstrating significant utility. Copy number variations may play dysregulation subunit expression. small molecule X4.5.dianilinophthalimide has shown promise targeted therapeutic agent pan-cancer context. Functional predictions indicate that implicated oxidative phosphorylation pathways proliferation-related pathways, including those mediated MYC, ASNS potentially acting an upstream regulator. Furthermore, been resistance drugs, gefitinib. In vitro experiments corroborate enhance malignant phenotypes through regulation Our novel insights into anti-cancer strategy underscores biomarker diagnosis, prognosis, prediction therapy responses.

Language: Английский

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Developing and validating a machine learning model to predict multidrug-resistant Klebsiella pneumoniae-related septic shock

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) infections pose a significant global healthcare challenge, particularly due to the high mortality risk associated with septic shock. This study aimed develop and validate machine learning-based model predict of MDR-KP-associated shock, enabling early stratification targeted interventions. A retrospective analysis was conducted on 1,385 patients MDR-KP admitted between January 2019 June 2024. The cohort randomly divided into training set (n = 969) validation 416). Feature selection performed using LASSO regression Boruta algorithm. Seven learning algorithms were evaluated, logistic chosen for its optimal balance performance robustness against overfitting. overall incidence shock 16.32% (226/1,385). predictive identified seven key factors: procalcitonin (PCT), sepsis, acute kidney injury, intra-abdominal infection, use vasoactive medications, ventilator weaning failure, mechanical ventilation. demonstrated excellent performance, an area under receiver operating characteristic curve (AUC) 0.906 in 0.865 set. Calibration robust, Hosmer-Lemeshow test results P 0.065 (training) 0.069 (validation). Decision indicated substantial clinical net benefit. presents validated, high-performing offering valuable tool decision-making. Prospective, multi-center studies are recommended further evaluate applicability effectiveness diverse settings.

Language: Английский

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DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

Damage-associated molecular patterns (DAMPs) induced by immunogenic cell death (ICD) may be useful for the immunotherapy to patients undergoing pancreatic ductal adenocarcinoma (PDAC). The aim of this study is predict prognosis and responsiveness PDAC using DAMPs-related genes. K-means analysis was used identify subtypes 175 cases. significance gene mutation immune status in different detected. LASSO regression construct a prognostic signature PDAC. Subsequently, vivo vitro experiments Bulk-RNA seq were verify effect hub pannexin 1 (PANX1) on Two clustered based expression levels DAMPs genes from patients. Besides, landscape up-regulated poor. In addition, we constructed that correlated with infiltration predicted or chemotherapy Mechanically, through sequencing experiments, found PANX1 promoted tumor progression regulation via ATP release active NOD1/NFκB signaling pathway Our silico analyses established classification system ICD-related PDAC, model efficacy immunotherapy. This will provide new perspective targeting molecule treatment

Language: Английский

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New insights into the mechanisms of the immune microenvironment and immunotherapy in osteosarcoma

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

Osteosarcoma, a malignant bone tumor primarily affecting adolescents, is highly invasive with poor prognosis. While surgery and chemotherapy have improved survival for localized cases, pulmonary metastasis significantly reduces to approximately 20%, highlighting the need novel treatments. Immunotherapy, which leverages immune system target osteosarcoma cells, shows promise. This review summarizes biological characteristics of osteosarcoma, mechanisms metastasis, microenvironment (TME). It involves recent immunotherapy advances, including monoclonal antibodies, vaccines, cell therapies, checkpoint inhibitors, oncolytic viruses, discusses combining these standard

Language: Английский

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Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 30, 2025

Background Glioblastoma, associated with poor prognosis and impaired immune function, shows potential interactions between newly identified disulfidptosis mechanisms T cell exhaustion, yet these remain understudied. Methods Key genes were using Lasso regression, followed by multivariate analysis to develop a prognostic model. Single-cell pseudotemporal explored T-cell exhaustion (Tex) signaling in differentiation. Immune infiltration was assessed via ssGSEA, while transwell assays immunofluorescence examined the effects of disulfidptosis-Tex on glioma behavior response. Results Eleven found critical for glioblastoma survival outcomes. This gene set underpinned model predicting patient prognosis. showed high activity endothelial cells. Memory populations linked genes. SMC4 inhibition reduced LN299 migration increased chemotherapy sensitivity, decreasing CD4 CD8 activation. Conclusions Disulfidptosis-Tex are pivotal progression interactions, offering new avenues improving anti-glioblastoma therapies through modulation exhaustion.

Language: Английский

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Prognostic value of body adipose tissue parameters in cancer patients treated with immune checkpoint inhibitors

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 12, 2025

Objective This study aims to explore the relationship between body adipose tissue characteristics and clinical outcomes in cancer patients receiving immune checkpoint inhibitor (ICI) therapy. Methods We conducted an extensive literature search across three major online databases—Embase, PubMed, Cochrane Library—to identify studies examining link treatment undergoing ICI therapy, from inception of each database until February 20, 2024. The quality included was evaluated using Newcastle-Ottawa Scale. primary analyzed were hazard ratios (HRs) for overall survival (OS) progression-free (PFS), as well odds (ORs) disease control rate (DCR). Pooled estimates 95% confidence intervals (CIs) calculated. Results A total 23 included, encompassing 2741 patients. analysis revealed that with higher levels visceral (VAT) exhibited significantly improved OS (HR: 0.72, CI: 0.59–0.89, p < 0.001) PFS 0.80, 0.67–0.96, = 0.015), along a DCR (OR: 1.81, 1.26–2.60, 0.001), compared those lower VAT levels. Additionally, increased subcutaneous (SAT) associated better 0.69, 0.58–0.82, 0.82, 0.68–1.00, 0.049), 1.99, 1.15–3.44, 0.014). Elevated (TAT) also linked longer 0.73, 0.55–0.97, 0.028). However, visceral-to-subcutaneous ratio (VSR) shorter 1.43, 1.09–1.87, 0.010). No significant found TAT 0.81, 0.54–1.23, 0.332) VSR 1.20, 0.95–1.51, 0.131) ICI-treated Conclusion highlights prognostic relevance SAT predicting response ICIs. These findings suggest assessments should be incorporated into evaluations this patient population.

Language: Английский

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Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

The isolation and application of biological macromolecules (BMMs) have become central in applied science today, with these compounds serving as anticancer, antimicrobial, anti-inflammatory agents. Parthenolide (PTL), a naturally occurring sesquiterpene lactone derived from Tanacetum parthenium (feverfew), is among the most important BMMs. PTL has been extensively studied for its anticancer properties, making it promising candidate further research drug development. This review summarizes effects derivatives, focus on Micheliolide (MCL) Dimethylaminomicheliolide (DMAMCL). These compounds, PTL, developed to overcome PTL's instability acidic basic conditions low solubility. We also explore their potential targeted combination therapies, providing comprehensive overview therapeutic mechanisms highlighting significance future cancer treatment strategies.

Language: Английский

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