Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level

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

Published: March 6, 2024

Background Glioblastoma (GBM), with its high recurrence and mortality rates, makes it the deadliest neurological malignancy. Oxidative phosphorylation is a highly active cellular pathway in GBM, NFYB tumor-associated transcription factor. Both are related to mitochondrial function, but studies on their relationship GBM at single-cell level still scarce. Methods We re-analyzed profiles of from patients different subtypes by transcriptomic analysis further subdivided large population Glioma cells into subpopulations, explored interrelationships pathways among cell stages clinical populations, investigated between factor key subpopulations searching for prognostic genes NFYB, verified experiments. Results C5 subpopulation had highest percentage G2M staging rGBM, which we hypothesized might be higher dividing proliferating ability both subpopulations. activity elevated subgroup, suggesting possible involvement proliferation recurrence, close association function. also identified 13 associated MEM60 may cause have poor prognosis promoting drug resistance. Knockdown was found contribute inhibition proliferation, invasion, migration cells. Conclusion These findings help elucidate mechanisms function progression establish new model therapeutic target based NFYB.

Language: Английский

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Deciphering the molecular landscape: integrating single-cell transcriptomics to unravel myofibroblast dynamics and therapeutic targets in clear cell renal cell carcinomas

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

Published: March 18, 2024

Background Clear cell renal carcinomas (ccRCCs) epitomize the most formidable clinical subtype among neoplasms. While impact of tumor-associated fibroblasts on ccRCC progression is duly acknowledged, a paucity literature exists elucidating intricate mechanisms and signaling pathways operative at individual cellular level. Methods Employing single-cell transcriptomic analysis, we meticulously curated UMAP profiles spanning substantial populations, delving into composition intrinsic these cohorts. Additionally, Myofibroblasts were fastidiously categorized discrete subpopulations, with thorough elucidation temporal trajectory relationships between subpopulations. We further probed interaction connecting pivotal subpopulations tumors. Our endeavor also encompassed identification prognostic genes associated through Bulk RNA-seq, subsequently validated empirical experimentation. Results A notable escalation in nFeature nCount EPCs within ccRCCs was observed, notably enriched oxidation-related pathways. This phenomenon postulated to be closely heightened metabolic activities EPCs. The subpopulation, denoted as C3 HMGA1+ Myofibroblasts, emerges subset, displaying low differentiation positioning itself terminal point trajectory. Intriguingly, cells exhibit high degree tumor MPZ pathway network, suggesting that may facilitate via this pathway. Prognostic identified, which TUBB3 implicated potential resistance recurrence. Finally, experimental validation revealed knockout key gene pathway, MPZL1, can inhibit activity, proliferation, invasion, migration capabilities. Conclusion investigation delves propose targeting MPZL1 oxidative phosphorylation could serve targets for treating recurrence ccRCC. discovery paves way new directions treatment prognosis diagnosis future.

Language: Английский

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Elucidating the role of tumor-associated ALOX5+ mast cells with transformative function in cervical cancer progression via single-cell RNA sequencing

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

Published: Aug. 19, 2024

Background Cervical cancer (CC) is the fourth most common malignancy among women globally and serves as main cause of cancer-related deaths in developing countries. The early symptoms CC are often not apparent, with diagnoses typically made at advanced stages, which lead to poor clinical prognoses. In recent years, numerous studies have shown that there a close relationship between mast cells (MCs) tumor development. However, research on role MCs played still very limited time. Thus, study conducted single-cell multi-omics analysis human cells, aiming explore mechanisms by interact microenvironment CC. goal was provide scientific basis for prevention, diagnosis, treatment CC, hope improving patients’ prognoses quality life. Method present acquired RNA sequencing data from ten samples ArrayExpress database. Slingshot AUCcell were utilized infer assess differentiation trajectory cell plasticity subpopulations. Differential expression subpopulations performed, employing Gene Ontology, gene set enrichment analysis, variation analysis. CellChat software package applied predict communication cells. Cellular functional experiments validated functionality TNFRSF12A HeLa Caski lines. Additionally, risk scoring model constructed evaluate differences features, prognosis, immune infiltration, checkpoint, across various scores. Copy number levels computed using inference copy variations. Result obtained 93,524 high-quality classified into types, including T_NK endothelial fibroblasts, smooth muscle epithelial B plasma MCs, neutrophils, myeloid Furthermore, total 1,392 subdivided seven subpopulations: C0 CTSG+ C1 CALR+ C2 ALOX5+ C3 ANXA2+ C4 MGP+ C5 IL32+ C6 ADGRL4+ MCs. Notably, subpopulation showed associations tumor-related results indicating resided intermediate-to-late stage differentiation, potentially representing crucial transition point benign-to-malignant transformation CNVscore bulk further confirmed transforming state subpopulation. revealed key receptor involved actions Moreover, vitro indicated downregulating may partially inhibit development prognosis infiltration based marker genes provided valuable guidance patient intervention strategies. Conclusions We first identified transformative tumor-associated within critical impacted progression inhibitory effect knocking down prognostic ALOX5+MCs subset demonstrated excellent predictive value. These findings offer fresh perspective decision-making

Language: Английский

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MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy

Translational Oncology, Journal Year: 2025, Volume and Issue: 52, P. 102280 - 102280

Published: Jan. 13, 2025

Language: Английский

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Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies

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

Published: Jan. 17, 2025

High-grade serous ovarian cancer (HGSOC), the predominant subtype of epithelial cancer, is frequently diagnosed at an advanced stage due to its nonspecific early symptoms. Despite standard treatments, including cytoreductive surgery and platinum-based chemotherapy, significant improvements in survival have been limited. Understanding molecular mechanisms, immune landscape, drug sensitivity HGSOC crucial for developing more effective personalized therapies. This study integrates insights from immunology, profiling, analysis identify novel therapeutic targets improve treatment outcomes. Utilizing single-cell RNA sequencing (scRNA-seq), systematically examines tumor heterogeneity microenvironment, focusing on biomarkers influencing response activity, aiming enhance patient outcomes quality life. scRNA-seq data was obtained GEO database this study. Differential gene expression analyzed using ontology set enrichment methods. InferCNV identified malignant cells, while Monocle, Cytotrace, Slingshot software inferred differentiation trajectories. The CellChat package predicted cellular communication between cell subtypes other pySCENIC utilized transcription factor regulatory networks within subtypes. Finally, results were validated through functional experiments, a prognostic model developed assess prognosis, infiltration, across various risk groups. investigated scRNA-seq, their interactions microenvironment. We confirmed key role C2 IGF2+ HGSOC, which significantly associated with poor prognosis high levels chromosomal copy number variations. located terminal tumor, displaying higher degree malignancy close association IIIC tissue types. also metabolic pathways, such as glycolysis riboflavin metabolism, well programmed death processes. highlighted complex fibroblasts MK signaling pathway, may be closely related tumor-associated progression. Elevated PRRX1 connected impact disease progression by modulating transcription. A based demonstrated adverse outcomes, emphasizing importance infiltration clinical intervention strategies. oncology, immunotherapy, reveal mechanisms driving resistance. subtype, linked offers promising target future Emphasizing sensitivity, research highlights strategies life patients.

Language: Английский

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Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

Background We explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict prognosis patients. Aberrant expression is associated with invasive behavior various tumors, including glioblastoma. However, specific role mechanisms are still unclear. Methods assessed RNA-seq microarray from TCGA GEO databases, combined scRNA-seq glioma patients GEO. Utilizing Seurat R package, we identified distinct survival-related gene clusters data. Prognostic pivotal genes were discovered through single-factor Cox analysis, a model was using LASSO stepwise regression algorithms. Moreover, investigated predictive potential these immune microenvironment their applicability immunotherapy. Finally, vitro experiments confirmed functional significance high-risk CRYAB. Results By analyzing ScRNA-seq data, 28 cell representing seven types. After dimensionality reduction clustering obtained four subpopulations within oligodendrocyte lineage trajectory. Using as marker for terminal-stage subpopulation, found that its poor prognosis. In demonstrated knocking out U87 LN229 cells reduced viability, proliferation, invasiveness. Conclusion The risk holds promise accurately predicting A comprehensive study would contribute understanding response Targeting may be beneficial

Language: Английский

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Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy

Translational Oncology, Journal Year: 2024, Volume and Issue: 52, P. 102255 - 102255

Published: Dec. 24, 2024

Language: Английский

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Novel insights into the interplay between m6A modification and programmed cell death in cancer

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(6), P. 1748 - 1763

Published: Jan. 1, 2023

N6-methyladenosine (m6A) methylation, the most prevalent and abundant RNA modification in eukaryotes, has recently become a hot research topic.Several studies have indicated that m6A is dysregulated during progression of multiple diseases, especially cancer development.Programmed cell death (PCD) an active orderly method development organisms, including apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis.As study PCD increasingly profound, accumulating evidence revealed mutual regulation PCD, their interaction can further influence sensitivity treatment.In this review, we summarize recent advances terms interplay potential mechanisms, as well therapeutic resistance.Our provides promising insights future directions for examination treatment cancers.

Language: Английский

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Non-apoptotic cell death programs in cervical cancer with an emphasis on ferroptosis

Critical Reviews in Oncology/Hematology, Journal Year: 2023, Volume and Issue: 194, P. 104249 - 104249

Published: Dec. 23, 2023

Language: Английский

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Combining bulk and scRNA‐seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(7)

Published: March 19, 2024

Abstract Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer‐related deaths. Unfortunately, many patients face issue inoperability at diagnostic phase to quite dismal prognosis. The onset metastatic processes has crucial role in elevated mortality rates linked PDAC. Individuals with advances receive only palliative therapy and have grim It essential carefully analyse intricacies process enhance prognosis for individuals Malignancy development greatly impacted by macrophage efferocytosis. Our current knowledge about complete range efferocytosis activities PDAC their intricate interactions tumour cells still restricted. This work aims resolve communication gaps pinpoint transcription factor that vital immunological response populations. We analysed eight tissue samples sourced from gene expression omnibus. utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat Monocle R together pySCENIC Python, single‐cell RNA sequencing (scRNA‐seq) data collected samples. study involved analysis comprehensive sample 22,124 cells, which were classified into distinct cell types. These types encompassed endothelial epithelial well various immune including CD4+ T CD8+ NK B plasma mast monocytes, DC different subtypes macrophages, namely C0 TGM2+, C1 PFN1+, C2 GAS6+ C3 APOC3+. differentiation between was achieved implementation CopyKat analysis, resulting detection categorization 1941 cells. amplification/deletion patterns observed on chromosomes differ significantly those Pseudotime Trajectories demonstrated subtype expressing TGM2+ had lowest level differentiation. Additionally, examination set scores related suggested this displayed higher activity during compared other subtypes. most active factors each identified BACH1, NFE2, TEAD4 ARID3A. In conclusion, human using immunofluorescence co‐localization CD68 CD11b within regions exhibiting presence keratin (KRT) alpha‐smooth muscle actin (α‐SMA). observation implies spatial association fibroblasts, There variation efferocytosis‐associated genes diversity might potentially influence advancement Moreover, central offers promising opportunity targeted immunotherapy treatment

Language: Английский

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