Evaluating the predictive value of angiogenesis-related genes for prognosis and immunotherapy response in prostate adenocarcinoma using machine learning and experimental approaches

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

Published: May 16, 2024

Background Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in development and advancement cancer. Although blocking angiogenesis has shown success treating different types solid tumors, its relevance prostate adenocarcinoma (PRAD) not been thoroughly investigated. Method This study utilized WGCNA method to identify angiogenesis-related genes assessed their diagnostic prognostic value patients with PRAD through cluster analysis. A model was constructed using multiple machine learning techniques, while developed employing LASSO algorithm, underscoring PRAD. Further analysis identified MAP7D3 as most significant gene among multivariate Cox regression various algorithms. The also investigated correlation between immune infiltration well drug sensitivity Molecular docking conducted assess binding affinity angiogenic drugs. Immunohistochemistry 60 tissue samples confirmed expression MAP7D3. Result Overall, 10 key demonstrated potential immune-related implications patients. is found be closely associated prognosis response immunotherapy. Through molecular studies, it revealed that exhibits high Furthermore, experimental data upregulation PRAD, correlating poorer prognosis. Conclusion Our important target

Language: Английский

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Identification of cancer stem cell-related genes through single cells and machine learning for predicting prostate cancer prognosis and immunotherapy

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

Published: Aug. 29, 2024

Background Cancer stem cells (CSCs) are a subset of within tumors that possess the unique ability to self-renew and give rise diverse tumor cells. These crucial in driving metastasis, recurrence, resistance treatment. The objective this study was pinpoint essential regulatory genes associated with CSCs prostate adenocarcinoma (PRAD) assess their potential significance diagnosis, prognosis, immunotherapy patients PRAD. Method utilized single-cell analysis techniques identify cell-related evaluate relation patient prognosis PRAD through cluster analysis. By utilizing datasets employing various machine learning methods for clustering, diagnostic models were developed validated. random forest algorithm pinpointed HSPE1 as most prognostic gene among genes. Furthermore, delved into association between immune infiltration, employed molecular docking investigate relationship its compounds. Immunofluorescence staining 60 tissue samples confirmed expression correlation Result This identified 15 analysis, highlighting importance diagnosing, prognosticating, potentially treating patients. specifically linked response immunotherapy, experimental data supporting upregulation poorer prognosis. Conclusion Overall, our findings underscore significant role unveil novel target related cell.

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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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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Exercise-downregulated CD300E acted as a negative prognostic implication and tumor-promoted role in pan-cancer

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

Published: July 31, 2024

Breast cancer ranks as one of the most prevalent malignancies among women globally, with increasing incidence rates. Physical activity, particularly exercise, has emerged a potentially significant modifier prognosis, influencing tumor biology and patient outcomes.

Language: Английский

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Unveiling the oncogenic role of CLDN11-secreting fibroblasts in gastric cancer peritoneal metastasis through single-cell sequencing and experimental approaches

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 129, P. 111647 - 111647

Published: Feb. 8, 2024

Language: Английский

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Multi-omic and machine learning analysis of mitochondrial RNA modification genes in lung adenocarcinoma for prognostic and therapeutic implications

Translational Oncology, Journal Year: 2025, Volume and Issue: 53, P. 102306 - 102306

Published: Feb. 4, 2025

Language: Английский

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Development of a novel prognostic signature based on cytotoxic T lymphocyte-evasion genes for hepatocellular carcinoma patient management

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

Published: Feb. 10, 2025

Cytotoxic T lymphocytes (CTLs) are major actors in innate and adaptive antitumor response. We attempted to apply cancer cell-intrinsic CTL evasion genes (CCGs) identify verify a risk stratification signature hepatocellular carcinoma (HCC) patients assess the prognosis benefits of immunotherapy, sorafenib treatment transcatheter arterial chemoembolization (TACE) treatment. developed novel prognostic including six CCGs was by LASSO Cox regression. CIBERSORT, quanTIseq, ssGSEA algorithms were used investigated correlation between CCG immune cell infiltration. also assessed performance predicting TACE with independent clinical mRNA sequencing data. The area under curve (AUC) for 1-, 3-, 5-year OS 0.77, 0.70 learning cohort, respectively. In external verification AUCs 0.71, 0.74 0.75. significantly positively related both TMB MSI. addition, responders had higher score than nonresponders when applied urothelial AUC response 0.65. further found that lower cohorts, 0.87 0.76, Finally, we identified four small molecule compounds negatively differentially expressed (DEGs) two categories HCC patients, monensin, etiocholanolone, naringenin, Prestwick-1103. has some significance may enhance patient outcomes even help develop strategies management.

Language: Английский

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Role of CD4+ T cells in cancer immunity: a single-cell sequencing exploration of tumor microenvironment

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 14, 2025

Recent oncological research has intensely focused on the tumor immune microenvironment (TME), particularly functions of CD4 + T lymphocytes. CD4+ lymphocytes have been implicated in antigen presentation, cytokine release, and cytotoxicity, suggesting their contribution to dynamics TME. Furthermore, application single-cell sequencing yielded profound insights into phenotypic diversity functional specificity cells In this review, we discuss current findings from analyses, emphasizing heterogeneity cell subsets implications immunology. addition, review critical signaling pathways molecular networks underpinning activities, thereby offering novel perspectives therapeutic targets strategies for cancer treatment prognosis.

Language: Английский

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PANoptosis‐Related Optimal Model (PROM): A Novel Prognostic Tool Unveiling Immune Dynamics in Lung Adenocarcinoma

International Journal of Genomics, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: PANoptosis, a recently characterized inflammatory programmed cell death modality orchestrated by the PANoptosome complex, integrates molecular mechanisms of pyroptosis, apoptosis, and necroptosis. Although this pathway potentially mediates tumor progression, its role in lung adenocarcinoma (LUAD) remains largely unexplored. Methods: Through comprehensive single-cell transcriptomic profiling, we systematically identified critical PANoptosis-associated gene signatures. Prognostic determinants were subsequently delineated via univariate Cox proportional hazards regression analysis. We constructed PANoptosis-related optimal model (PROM) through integration 10 machine learning algorithms. The was initially developed using Cancer Genome Atlas (TCGA)-LUAD cohort validated across six independent LUAD cohorts. Model performance evaluated mean concordance index. Furthermore, conducted extensive multiomics analyses to delineate differential activation patterns immune infiltration profiles between PROM-stratified risk subgroups. Results: Cellular populations exhibiting elevated PANoptosis signatures demonstrated enhanced intercellular signaling networks. PROM superior prognostic capability multiple validation Receiver operating characteristic curve revealed area under values exceeding 0.7 all seven cohorts, with several achieving above 0.8, indicating robust discriminative performance. score exhibited significant correlation immunological parameters. Notably, high scores associated attenuated responses, suggesting an immunosuppressive microenvironment. Multiomics investigations alterations oncogenic pathways landscape Conclusion: This investigation establishes as clinically applicable tool for stratification. Beyond predictive utility, elucidates biological underlying progression. These findings provide novel mechanistic insights into pathogenesis may inform development targeted therapeutic interventions personalized treatment strategies optimize patient outcomes.

Language: Английский

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