Single-cell sequencing analysis related to sphingolipid metabolism guides immunotherapy and prognosis of skin cutaneous melanoma

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

Published: Nov. 23, 2023

Background We explore sphingolipid-related genes (SRGs) in skin melanoma (SKCM) to develop a prognostic indicator for patient outcomes. Dysregulated lipid metabolism is linked aggressive behavior various cancers, including SKCM. However, the exact role and mechanism of sphingolipid remain partially understood. Methods integrated scRNA-seq data from patients sourced GEO database. Through utilization Seurat R package, we successfully identified distinct gene clusters associated with survival data. Key were through single-factor Cox analysis used model using LASSO stepwise regression algorithms. Additionally, evaluated predictive potential these within immune microenvironment their relevance immunotherapy. Finally, validated functional significance high-risk IRX3 vitro experiments. Results Analysis expression patterns 4 specific diverse cell subpopulations. Re-clustering cells based on increased SRG revealed 7 subgroups significant implications. Using marker genes, lasso, regression, selected 11 construct risk signature. This signature demonstrated strong correlation infiltration stromal scores, highlighting its tumor microenvironment. Functional studies involving knockdown A375 WM-115 showed reductions viability, proliferation, invasiveness. Conclusion SRG-based holds promise precise prognosis. An in-depth exploration characteristics offers insights into immunotherapy response. Therapeutic targeting may benefit patients.

Language: Английский

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Decoding the tumor microenvironment and molecular mechanism: unraveling cervical cancer subpopulations and prognostic signatures through scRNA-Seq and bulk RNA-seq analyses

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

Published: Feb. 28, 2024

Background Cervical carcinoma (CC) represents a prevalent gynecological neoplasm, with discernible rise in prevalence among younger cohorts observed recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated. Methods We utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize tumor epithelial cells derived from four specimens cervical patients. This method enabled identification pivotal subpopulations and elucidation their contributions progression. Subsequently, we assessed influence associated molecules bulk (Bulk RNA-seq) performed experiments for validation purposes. Results Through our analysis, have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as noteworthy subpopulation (CC), exerting on differentiation progression CC. established an independent prognostic indicator—the EPCs score. By stratifying patients into high low score groups based median score, that high-score group exhibits diminished survival rates compared low-score group. The correlations between these immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, other factors, further underscore impact prognosis. Cellular validated significant ATF6 proliferation migration cell lines. Conclusion study enriches comprehension determinants shaping CC, elevates cognizance microenvironment offers valuable insights prospective therapies. These discoveries contribute refinement diagnostics formulation optimal therapeutic approaches.

Language: Английский

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Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer

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

Published: July 29, 2024

Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains significant challenge achieving optimal tumor control. However, the exploration of intratumoral heterogeneity malignant epithelial cells ovarian cancer microenvironment still limited, hindering our comprehensive understanding disease.

Language: Английский

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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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Integrative Single-Cell Analysis of Cardiomyopathy Identifies Differences in Cell Stemness and Transcriptional Regulatory Networks among Fibroblast Subpopulations

Cardiology Research and Practice, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 22

Published: May 18, 2024

Cardiomyopathy encompasses a broad spectrum of diseases affecting myocardial tissue, characterized clinically by abnormalities in cardiac structure, heart failure, and/or arrhythmias. Clinically heterogeneous, major types include dilated cardiomyopathy (DCM), hypertrophic (HCM), restrictive (RM), ischemic (ICM), among which DCM is more prevalent, while ICM exhibits higher incidence and mortality rates. Myocardial injury during progression may lead to fibrosis. Failure intervene early inhibit the process fibrosis culminate failure. Cardiac fibroblasts constitute crucial cellular components determining extent quality fibrosis, with various subpopulations exerting diverse roles progression. Despite this, understanding plasticity transcriptional regulatory networks remains limited. Therefore, this study, we conducted comprehensive single-cell analysis explore differences fibroblast subpopulations, aim providing as many useful references possible for diagnosis, prognosis, treatment cardiomyopathy. Cells mitochondrial gene expression comprising >20% total expressed genes were excluded. Differential (DEGs) stemness within subjected Gene Ontology (GO) biological processes (BP) AUCell analysis. Monocle software was employed analyze pseudo-temporal trajectory Additionally, Python package SCENIC utilized assess enrichment transcription factors activity regulators Following batch effect correction, 179,927 cells clustered into 32 clusters, designated T_NK cells, endothelial myeloid fibroblasts, pericytes, SMCs, CMs, proliferating EndoCs, EPCs. Among them, 8148 further subdivided 4 namely C0 THBS4+ Fibroblasts, C1 LINC01133+ C2 FGF7+ C3 AGT + Fibroblasts. Results from GO_BP analyses suggest that Fibroblasts be associated immune response activation, protein transport, contractile function, correlating disease Transcription factor indicates FOS most significant TF also M1 module, possibly implicated hydrolysis, intracellular DNA replication, cell proliferation. Moreover, correlation between reveals pronounced heterogeneity exhibit increased sensitivity towards adverse outcomes cardiomyopathy, such impaired compared other subpopulations. The differential subgroups offer new perspectives targeting subpopulation treat EPAS1 MYC, along regulator FOS, play modulating

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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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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Unveiling the cellular landscape: insights from single-cell RNA sequencing in multiple myeloma

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

Published: Aug. 30, 2024

The aim of this research was to gain a thorough understanding the processes involved in cell communication and discover potential indicators for treating multiple myeloma (MM) through use single-cell RNA sequencing (scRNA-seq). And explored expression myeloma-related subgroups on metal ion-related pathways explore relationship between MM ions.

Language: Английский

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Single-cell RNA sequencing explored potential therapeutic targets by revealing the tumor microenvironment of neuroblastoma and its expression in cell death

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 5, 2024

Language: Английский

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