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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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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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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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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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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Single-cell sequencing uncovers the mechanistic role of DAPK1 in glioma and its diagnostic and prognostic implications

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

Published: Jan. 24, 2025

Background We conducted an investigation into the characteristics of single-cell differentiation data in gliomas, with a focus on developing DAPK1-based prognostic markers to predict patient outcomes. Dysregulated expression DAPK1 has been associated invasive behavior various malignancies, including gliomas. However, precise role and underlying mechanisms gliomas remain inadequately understood. Methods performed analyses RNA-seq microarray datasets from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO), addition RNA sequencing (scRNA-seq) glioma patients available GEO. Utilizing Seurat R package, we identified gene clusters survival scRNA-seq data. Prognostic models were developed using LASSO stepwise regression algorithms. Furthermore, assessed predictive potential these genes within immune microenvironment their relevance immunotherapy contexts. Results Our analysis revealed 32 distinct cell corresponding 10 types. Through dimensionality reduction clustering, three glial subpopulations based trajectories. DAPK1, serving as marker for terminal subpopulation, exhibited association poor prognosis. Conclusions show promise accurately predicting outcomes glioblastoma glioma. An in-depth examination DAPK1’s specific could elucidate its response. Targeting may offer therapeutic benefits patients.

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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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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Inhibition of programmed cell death by melanoma cell subpopulations reveals mechanisms of melanoma metastasis and potential therapeutic targets

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 20, 2025

Melanoma is an aggressive type of skin cancer that arises from melanocytes, the cells responsible for producing pigment. In contrast to non-melanoma cancers like basal cell carcinoma and squamous carcinoma, melanoma more invasive. was distinguished by its rapid progression, high metastatic potential, significant resistance conventional therapies. Although it accounted a small proportion cases, accounts majority deaths caused due ability invade deep tissues, adapt diverse microenvironments, evade immune responses. These unique features highlighted challenges treating underscored importance advanced tools, such as single-cell sequencing, unravel biology develop personalized therapeutic strategies. Thus, we conducted analysis cellular composition within tumor tissues further subdivided into subpopulations. Through analyzing metabolic pathways, stemness genes, transcription factors (TFs) among in different phases (G1, G2/M, S) well between primary foci cells, investigated specific mechanisms underlying metastasis. We also revisited temporal trajectories subpopulations, identifying core subpopulation C0 SOD3 + cells. Our findings revealed close relationship pivotal oxidative pathways tissues. Additionally, analyzed prognostically relevant differentially expressed genes (DEGs) built predictive model associated with outcomes. selected gene IGF1 highest coefficient (coef) value analysis, experimentally validated essential function proliferation invasive metastasis melanoma. infiltration discovered critical roles played M1/M2 macrophages progression evasion. Furthermore, development malignant were closely various forms programmed death (PCD), including apoptosis, autophagic death, ferroptosis, pyroptosis. often resisted mechanisms, maintaining their growth inhibiting apoptosis evading death. Meanwhile, induction ferroptosis pyroptosis thought trigger responses helped suppress dissemination. A deeper understanding PCD provided foundation developing novel targeted therapies, potential enhance treatment efficacy. contributed prognostic models shed light on research directions concerning targets.

Language: Английский

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Single-cell RNA sequencing revealed PPARG promoted osteosarcoma progression: based on osteoclast proliferation

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

Published: Jan. 28, 2025

Background Osteosarcoma (OS) is one of the most common primary malignant bone tumors, primarily originating from mesenchymal tissue. It notorious for its high invasiveness, disability rate, mortality and poor prognosis. In metastatic destruction can promote cancer progression, which closely related to osteoclast activation imbalance between osteoblasts osteoclasts. A large number studies confirmed that osteoclasts are an important part OS, play active role in destroying homeostasis promoting progress OS. Therefore, we conducted a detailed study at single cell level, aiming find new OS therapeutic targets prevent tumor progression local spread. Methods We analyzed single-cell sequencing data patients usedMonocle2, Cytotrace, Slingshot software analyze pseudo-sequential trajectory during progression. CellChat was used reveal communication cells. PySCENIC identify transcription factors Finally, further demonstrated results by RT-qPCR analysis, CCK-8 assay, wound healing Transwell etc. Results Through analysis identified highly specific subgroup, C2MKI67+ Osteoclast. The key signaling pathway APP top 1 factor PPARG this subgroup played essential roles proliferation differentiation. Given pivotal speculated these pathways could emerge as novel targets, offering innovative strategies treatment. Conclusion This enhanced our understanding through scRNA-seq. Furthermore, discovered amplifies proliferation, resulting excessive resorption degradation matrix, thereby creating favorable environment growth. By innovatively targeting PPARG, it affected thus progression; work offered insights directions clinical treatment patients.

Language: Английский

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