Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: April 9, 2025
Language: Английский
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 7, 2025
Cervical cancer is the fourth most common in women globally, and main cause of disease has been found to be ongoing HPV infection. remains primary cancer-related death despite major improvements screening treatment approaches, especially low- middle-income nations. Therefore, it crucial investigate tumor microenvironment advanced cervical order identify possible targets. In better understand malignant epithelial cells (EPCs), this study used bulk RNA-seq data from UCSC conjunction with single-cell RNA sequencing ArrayExpress database. After putting quality control procedures into place, cell type identification clustering analysis using Seurat software were carried out. To clarify functional pathways, enrichment differential gene expression The CIBERSORT ESTIMATE R packages evaluate immune characteristics, univariate multivariate Cox regression analyses extract prognostic features. Furthermore, assessments drug sensitivity Eight types identified, EPCs showing high proliferative stemness Five EPC subpopulations defined, C1 NNMT+ CAEPCs driving differentiation. A NNMT Risk Score (NCRS) model was developed, revealing a correlation between elevated NCRS scores adverse patient outcomes characterized by evasion. vitro experiments validated that PLOD2 significantly enhances proliferation, migration, invasion cells. This investigation delineated eight five cancer, establishing as therapeutic target. demonstrated its capability, indicating higher are associated poorer clinical outcomes. validation highlights potential, underscoring critical need for integrating immunotherapy targeted strategies enhance diagnostic approaches cancer.
Language: Английский
Citations
5
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
Citations
2
Cancer Control, Journal Year: 2024, Volume and Issue: 31
Published: Jan. 1, 2024
The goal of this study was to evaluate the global burden malignant skin melanoma (MSM) from 1990 2019 using MSM-related data Global Burden Disease study.
Language: Английский
Citations
9
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
Citations
1
Translational Oncology, Journal Year: 2024, Volume and Issue: 52, P. 102255 - 102255
Published: Dec. 24, 2024
Language: Английский
Citations
7
Translational Oncology, Journal Year: 2024, Volume and Issue: 43, P. 101910 - 101910
Published: Feb. 27, 2024
Immune checkpoint inhibitors (ICB) therapy have emerged as effective treatments for melanomas. However, the response of melanoma patients to ICB has been highly heterogenous. Here, by analyzing integrated scRNA-seq datasets from patients, we revealed significant differences in TiME composition between ICB-resistant and responsive tissues, with resistant or tissues characterized an abundance myeloid cells CD8+ T CD4+ cell predominance, respectively. Among cells, CXCL13+ Tfh-like were associated immunosuppressive phenotype linked immune escape-related genes negative regulation activation. We also develop immunotherapy prediction model based on compartment. Our predictive was validated using CIBERSORTx bulk RNA-seq pre- post-ICB treatment showed a better performance than other existing models. study presents potential further translation, well underscores critical role influencing melanomas immunotherapy.
Language: Английский
Citations
4
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
Citations
4
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 15, 2025
The characteristics and role of NOD-like receptor (NLR) signaling pathway in high-grade gliomas were still unclear. This study aimed to reveal the association NLR with clinical heterogeneity glioblastoma (GBM) patients, explore hub genes occurrence development GBM. Transcriptomic data from 496 GBM patients complete prognostic information obtained TCGA, GEO, CGGA databases. Using NMF clustering algorithm expression profiles genes, these classified into different subtypes. activity immune micro-environment then compared between A novel accurate profile-based marker for was developed using LASSO COX regression analysis. Based on gene profile, accurately divided two subtypes (C1 C2) outcomes. groups showed microenvironment metabolic characteristics, which might be potential reason difference prognosis. Differential enrichment analyzes revealed intrinsic signature differences C1 C2 differential C2, molecular markers related developed. AUC value 3-year ROC curve ranged 0.601 0.846, suggesting its significance. Single-cell sequencing analysis that mainly active myeloid cells within random forest identified crucial TRIP6 pathway. Molecular biology experiments confirmed abnormally overexpressed Knockdown can significantly inhibit proliferation migration ability cells. plays a critical regulating metabolism reprogramming is affects malignant biological behavior
Language: Английский
Citations
0
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
Citations
0
Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)
Published: Jan. 1, 2025
Abstract Dysregulated mitophagy is essential for mitochondrial quality control within human cancers. However, identifying hub genes regulating and developing mitophagy‐based treatments to combat drug resistance remains challenging. Herein, BayeDEM (Bayesian‐optimized Deep learning Essential of Mitophagy) was proposed such a task. After Bayesian optimization, demonstrated its excellent performance in critical osteosarcoma (area under curve [AUC] ROC: 98.96%; AUC PR curve: 100%). CERS1 identified as the most gene (mean (|SHAP value|): 4.14). Inhibition sensitized cisplatin‐resistant cells cisplatin, restricting their growth, proliferation, invasion, migration colony formation inducing apoptosis. Mechanistically, inhibition restricted destroy cells, including membrane potential loss unfavourable dynamics, rendering them susceptible cisplatin‐induced More importantly, facilitated immunosuppressive microenvironment by significantly modulating T‐cell differentiation, adhesion antigen presentation, mainly affects malignant osteoblasts early‐mid developmental stage. Immunologically, potentially modulated MIF signalling transmission between B DCs, CD8+ T NK monocytes through MIF‐(CD74 + CXCR4) receptor–ligand interaction, thereby biological functions these immune cells. Collectively, emerged promising tool oncologists identify pivotal governing mitophagy, enabling mitophagy‐centric therapeutic strategies counteract resistance.
Language: Английский
Citations
0