Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer

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

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AXL: shapers of tumor progression and immunosuppressive microenvironments

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 11, 2025

As research progresses, our understanding of the tumor microenvironment (TME) has undergone profound changes. The TME evolves with developmental stages cancer and implementation therapeutic interventions, transitioning from an immune-promoting to immunosuppressive microenvironment. Consequently, we focus intently on significant role in proliferation, metastasis, development drug resistance. AXL is highly associated progression; however, previous studies have been limited its impact biological behavior cells. An increasing body now demonstrates that can influence function differentiation immune cells, mediating suppression thereby fostering growth. A comprehensive analysis identify overcome causes microenvironments represents a novel approach conquering cancer. In this review, elucidating within microenvironments, discussing analyzing effects T macrophages, natural killer (NK) fibroblasts, other immune-stromal We aim clarify contributions progression resistance functional

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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Comprehensive single-cell pan-cancer atlas unveils IFI30+ macrophages as key modulators of intra-tumoral immune dynamics

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

Published: Jan. 24, 2025

Background The convergence of macrophage-targeted strategies with immune checkpoint blockade therapies defines a pivotal avenue in contemporary tumor therapy. Identifying robust genetic regulators this context is imperative. Methods This study elucidates IFI30's role enhancing Major Histocompatibility Complex II (MHC-II) restriction antigen processing. Despite its recognition cancer immunotherapy, IFI30 remains nascent focus. Our approach involves multi-omics analysis immunological profile the macrophage-mediated Tumor Microenvironment (TME), spanning various cancers and bolstered by rigorous co-culture laboratory work. Results predominantly localizes monocyte/macrophage populations, correlating strongly cell infiltration. Substantiated single-cell analysis, exhibits significant functional enrichment immune-related pathways. Co-expression genes, including MHC elements checkpoints, further validates relevance. Conclusion positions as promising immunotherapeutic target. Pan-cancer analyses glioblastoma multiforme (GBM) investigations collectively underscore potential TME modulator, particularly interaction M2-macrophages. emerges prospective intervention point landscape.

Language: Английский

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Preoperative inflammatory markers and tumor markers in predicting lymphatic metastasis and postoperative complications in colorectal cancer: a retrospective study

BMC Surgery, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 18, 2025

To analyze the impact of preoperative inflammatory markers and tumor on lymphatic metastasis postoperative complications in colorectal cancer patients, explore their predictive value for these outcomes. Furthermore, based marker indicators with significant effects, models risk incidence will be constructed. This study retrospectively analyzed clinical data CRC patients who underwent surgical treatment at Shanxi Bethune Hospital between January 2021 June 2024. Preoperative were compared lymph node-positive node-negative groups. Variables selected using Lasso regression, independent factors influencing node identified through multivariate logistic regression analysis. Based results, a Nomogram prediction model was constructed, its accuracy evaluated calibration curve. The discriminatory ability assessed ROC curve, applicability DCA Similarly, predicting complications, Pearson correlation analysis used to examine relationships markers, complications. curves employed calculate AUC optimal cutoff values each marker. Kaplan-Meier (KM) DFS. Independent univariate analyses, constructed validated. A total 196 included study. NLR, PLR, FAR, CEA, CA199, CA724 levels significantly elevated group (P < 0.05). smoking history, as non-zero coefficient variables. Multivariate further confirmed history (HR = 4.20), NLR 2.52), FAR 1.18), 1.32) predictors results showed high accuracy, curve 0.880, indicating excellent ability. decision demonstrated good applicability. In complication prediction, revealed positive rates 0.05), coefficients 0.24, 0.34, 0.16, 0.19, respectively, PLR showing strongest correlation. that AUCs LMR, CAR 0.633, 0.675, 0.467, 0.580, 0.559, 4.29, 261.71, 3.39, 18.20, 11.26, respectively. 0.567, 0.612, 0.609, 11.87, 10.27, 6.85. KM higher CAR, associated poorer Univariate 1.53) 1.11) indicated 0.729, demonstrating ability, have occurrence certain developed this provide reference personalized diagnosis treatment, but practical application needs validated large-scale studies.

Language: Английский

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The biological roles and molecular mechanisms of m6A reader IGF2BP1 in the hallmarks of cancer

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101567 - 101567

Published: Feb. 1, 2025

Language: Английский

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The role of tumor-associated macrophages in lung cancer

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

Published: Feb. 26, 2025

Lung cancer remains a leading cause of cancer-related deaths worldwide, necessitating innovative treatments. Tumor-associated macrophages (TAMs) are primary immunosuppressive effectors that foster tumor proliferation, angiogenesis, metastasis, and resistance to therapy. They broadly categorized into proinflammatory M1 tumor-promoting M2 phenotypes, with elevated infiltration correlating poor prognosis. Strategies aimed at inhibiting TAM recruitment, depleting TAMs, or reprogramming therefore highly promising. Key signaling pathways, such as CSF-1/CSF-1R, IL-4/IL-13-STAT6, TLRs, CD47-SIRPα, regulate polarization. Additionally, macrophage-based drug delivery systems permit targeted agent transport hypoxic regions, enhancing Preclinical studies combining TAM-targeted therapies chemotherapy immune checkpoint inhibitors have yielded improved responses prolonged survival. Several clinical trials also reported benefits in previously unresponsive patients. Future work should clarify the roles macrophage-derived exosomes, cytokines, additional mediators shaping microenvironment. These insights will inform design next-generation carriers optimize combination immunotherapies within precision medicine frameworks. Elucidating phenotypes their regulatory molecules central developing novel strategies curb progression ultimately improve outcomes lung cancer. Importantly, immunomodulation may offer expanded treatment avenues.

Language: Английский

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Expression patterns of MCM8 in lung adenocarcinoma and its correlation with key biological processes

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: March 3, 2025

Lung adenocarcinoma (LUAD) is one of the most common and lethal tumors. The identification diagnostic prognostic biomarkers essential to improve patient prognosis treatment outcomes. expression minichromosome maintenance complex component 8 (MCM8) in 33 cancer types was analyzed using Cancer Genome Atlas (TCGA) Genotype-Tissue Expression. Tumor normal tissues LUAD were compared TCGA data validated against four datasets from Gene Expression Omnibus. MCM8 assessed by immunohistochemistry (IHC) tissue microarrays. value Receiver Operating Characteristic curve analysis, its significance determined Kaplan–Meier analysis. CIBERSORT method used examine immune infiltration. association between m6A RNA methylation, glycolysis, ferroptosis GEPIA online tool. markedly overexpressed many tumors including LUAD. showed high accuracy for diagnosis LUAD, with an area under 0.849 dataset. overexpression tumor confirmed IHC shown be associated decreased overall survival disease-specific survival. Analysis cell infiltration that populations differed low groups. correlated genes ferroptosis. identified as a promising marker mechanism underlying effect on development response remains elucidated.

Language: Английский

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Single-cell insights into HNSCC tumor heterogeneity and programmed cell death pathways

Translational Oncology, Journal Year: 2025, Volume and Issue: 54, P. 102341 - 102341

Published: March 10, 2025

Language: Английский

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Investigation of sphingolipid-related genes in lung adenocarcinoma

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: March 13, 2025

Background Lung adenocarcinoma (LUAD) is responsible for majority cases of lung cancer and considered to be the primary cause cancer-related mortality. The imbalance cellular proliferation apoptosis critically implicated in pathogenesis progression LUAD. Sphingomyelin, a vital lipid component, integral regulation tumor cell growth apoptosis, has garnered significant attention as target novel anticancer therapies. pivotal molecules involved sphingomyelin metabolism are crucial modulating behavior, thereby influencing clinical outcomes. Methods A comprehensive consensus clustering analysis was conducted by collecting LUAD figures from TCGA GEO databases. By employing Cox regression Lasso analysis, prognostic model patients established identifying seven sphingolipid-related genes (SRGs), validated database. study also delved into relevance, functional capabilities, immune implications signals associated with sphingolipid metabolism. Finally, experiments vitro confirmed sphingolipid-associated Results Using model, can divided high-risk low-risk groups. Meanwhile, we observe marked disparities survival times among these Additionally, demonstrates high predictive accuracy external validation cohorts. Research on microenvironment immunotherapy points this risk stratification useful reference immunotherapeutic strategies our hypothesis corroborated through experiments. Conclusion This that gene characteristics correlate recurrence, long-term prognosis, infiltration patients. outcomes could help shape innovative early intervention prognosis prediction adenocarcinoma.

Language: Английский

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