Identification of lipid metabolism related immune markers in atherosclerosis through machine learning and experimental analysis

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

Published: Feb. 25, 2025

Atherosclerosis is a significant contributor to cardiovascular disease, and conventional diagnostic methods frequently fall short in the timely accurate detection of early-stage atherosclerosis. Abnormal lipid metabolism plays critical role development Consequently, identification new markers essential for precise diagnosis this condition. The datasets related atherosclerosis utilized research were obtained from GEO database (GSE2470, GSE24495, GSE100927 GSE43292). ssGSEA technique was first assess scores samples affected by atherosclerosis, thereby aiding discovery important regulatory genes linked via WGCNA. Following this, differential expression analysis functional evaluations carried out, after which various machine learning approaches employed determine A model then developed validated through several algorithms. Furthermore, molecular docking studies conducted analyze binding affinity these key with therapeutic agents also used measure immune cell atherosclerotic samples, exploration connection between cells. Finally, variations identified pivotal confirmed experimental validation. WGCNA 302 metabolism-related revealed that are associated multiple pathways. Through further screening using algorithms, APLNR, PCDH12, PODXL, SLC40A1, TM4SF18, TNFRSF25 as we constructed predict occurrence high accuracy, indicated six have potential drug targets. Additionally, algorithm association levels experimentally confirmed. Our study introduces novel emphasizes their immune-related This provides valuable approach predictive targeted therapy

Language: Английский

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The role of endothelial cell-related gene COL1A1 in prostate cancer diagnosis and immunotherapy: insights from machine learning and single-cell analysis

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 8, 2025

Endothelial cells are integral components of the tumor microenvironment and play a multifaceted role in immunotherapy. Targeting endothelial related signaling pathways can improve effectiveness immunotherapy by normalizing blood vessels promoting immune cell infiltration. However, to date, there have been no comprehensive studies analyzing diagnosis treatment prostate adenocarcinoma (PRAD). By integrating clinical transcriptomic data from TCGA-PRAD, we initially identified key cell-related genes PRAD samples through single-cell analysis. Subsequently, cluster analysis was employed classify based on expression these genes, allowing us explore their correlation with patient prognosis outcomes. A diagnostic model then constructed validated using combination 108 machine learning algorithms. The XGBoost Random Forest algorithms highlighted significant COL1A1, further analyzed AR, EGFR multiplex immunofluorescence staining. In vitro experimental impact COL1A1 progression PRAD. Single-cell 12 differential prognostic associated cells. Cluster confirmed strong between both cancer responses. Diagnostic models developed various techniques demonstrated predictive capability cancer. Furthermore, patients' information, multiple analyses critical COL1A1. Immunofluorescence results that is highly expressed positively correlated AR EGFR. experiments confirm reducing levels inhibit progression. This study provides diagnosis, prognosis, findings, supported results, highlight as target for

Language: Английский

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Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide

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

Published: Feb. 20, 2025

The isolation and application of biological macromolecules (BMMs) have become central in applied science today, with these compounds serving as anticancer, antimicrobial, anti-inflammatory agents. Parthenolide (PTL), a naturally occurring sesquiterpene lactone derived from Tanacetum parthenium (feverfew), is among the most important BMMs. PTL has been extensively studied for its anticancer properties, making it promising candidate further research drug development. This review summarizes effects derivatives, focus on Micheliolide (MCL) Dimethylaminomicheliolide (DMAMCL). These compounds, PTL, developed to overcome PTL's instability acidic basic conditions low solubility. We also explore their potential targeted combination therapies, providing comprehensive overview therapeutic mechanisms highlighting significance future cancer treatment strategies.

Language: Английский

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Prognostic significance and immune microenvironment infiltration patterns of hypoxia and endoplasmic reticulum stress-related genes in gastric cancer

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

Published: Feb. 21, 2025

Gastric cancer (GC) is a prevalent malignant neoplasm within the digestive system, accounting for approximately 740,000 deaths globally each year, significantly impacting patients' quality of life and survival rates. The objective this investigation was to elucidate expression patterns Hypoxia Endoplasmic Reticulum Stress-related Differentially Expressed Genes (HERSRDEGs) in GC their association with prognostic outcomes patients. Utilizing Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases, datasets were retrieved, standard normalization performed. Differential analysis conducted using DESeq2, while somatic mutations copy number variations examined maftools GISTIC2.0. Spearman's correlation assessed interplay between HERSRDEGs across datasets. Functional enrichment analyses carried out clusterProfiler Ontology (GO) Kyoto Encyclopedia Genomes (KEGG) pathways, alongside Set Enrichment Analysis (GSEA). A risk model obtained by utilizing univariate Cox regression R package. We employed RT-qPCR validate mRNA levels five genes that impact gastric human adenocarcinoma tissues. acquired data revealed 19 including ANGPT2, CXCL8, AURKA exhibiting significant variation controls. In analysis, total genes-ANGPT2, CD36, EGR1, NOX4, TLR2-emerged as statistically significant, correlating strongly overall survival. LASSO featuring NOX4 yielded score formula capable predicting patient outcomes. Furthermore, multivariate highlighted RiskScore, age stage predictors. immune infiltration notable differences populations cells, such Natural Killer cells T-helper when comparing high-risk low-risk groups. conclusion, elucidates involvement progression potential biomarkers.

Language: Английский

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Zinc finger protein ZC3H18 is abnormally expressed in esophageal cancer tissues and facilitates the proliferation of esophageal cancer cells

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

Published: Feb. 25, 2025

Esophageal cancer presents significant challenges due to the limited efficacy and severe side effects associated with conventional treatments. The identification of epigenetic regulatory molecules that are aberrantly expressed in tumors is crucial for elucidating mechanisms underlying development progression esophageal cancer. We performed high-throughput methylation level analysis on cancerous adjacent tissues from 25 patients, identifying differentially methylated gene ZC3H18 utilizing Bismark software data TCGA. cell lines knockdown were used validate biological role tumorigenesis vitro vivo. Eukaryotic transcriptome sequencing was conducted investigate potential function. identified 30 genes exhibiting differences between non-cancerous patients. Subsequent TCGA database revealed tumor closely patient prognosis. Examination tissue samples demonstrated overexpression protein, which positively correlated adverse prognosis indicators, including differentiation, stage, invasion depth. significantly inhibited cellular proliferation, migration, invasion, damage repair. Additionally, promoted growth expression various cytokeratins reduced following knockdown. multiple keratins co-localized tissue. exhibits differential unfavorable plays a critical regulation functions within tumors.

Language: Английский

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Mechanisms of tumor-associated macrophages in breast cancer and treatment strategy

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

Published: Feb. 28, 2025

Breast cancer (BC) is the most common in women and a leading cause of cancer-related mortality. Despite advances screening treatment, outcomes for advanced or recurrent BC remain poor, highlighting need new strategies. Recent research emphasizes tumor microenvironment (TME), particularly tumor-associated macrophages (TAMs), as key drivers growth, metastasis, resistance to therapy. The presence M2-like TAMs TME promotes immune evasion progression across subtypes. This review summarizes classification, their role BC, emerging therapies targeting TAMs, including depletion, inhibition recruitment, reprogramming from pro-tumoral M2 anti-tumoral M1 phenotypes. Targeting offers promising strategy improve treatment outcomes.

Language: Английский

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Metabolic reprogramming shapes the immune microenvironment in pancreatic adenocarcinoma: prognostic implications and therapeutic targets

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

Published: March 21, 2025

Introduction Pancreatic adenocarcinoma (PAAD) is characterized by a profoundly immunosuppressive tumor microenvironment (TME) that limits the efficacy of immunotherapy. Emerging evidence suggests tumor-specific metabolic reprogramming may drive disease progression and shape immune landscape in PAAD. Methods We integrated multi-omics data from TCGA, GEO, ICGC to identify key metabolism-related genes (MRGs) influence cell infiltration, progression, patient survival. Based on nine pivotal MRGs (including ANLN, PKMYT1, HMGA1), we developed validated novel metabolic-prognostic index (MPI). Functional enrichment analyses were conducted elucidate pathways associated with different MPI risk groups. In vitro experiments drug sensitivity performed confirm oncogenic role selected explore their therapeutic implications. Results The effectively stratified patients into high- low-risk High-MPI scores correlated poor overall survival, elevated mutation burden (TMB), an TME, evidenced reduced CD8⁺ T-cell infiltration increased expression checkpoints (PD-L1, TGF-β). revealed glycolysis folate biosynthesis as dominant high-MPI groups, whereas fatty acid metabolism prevailed low-MPI Experimental validation underscored ANLN promoting epithelial-mesenchymal transition (EMT) evasion via NF-κB signaling. knockdown significantly glycolytic activity, migration, evasion. Drug indicated resistance gemcitabine but afatinib patients. Although TIDE analysis predicted checkpoint inhibitor (ICI) tumors, subset showed favorable responses anti-PD-L1 therapy. Discussion These findings provide comprehensive framework for understanding how shapes PAAD’s TME affects treatment outcomes. By accurately stratifying patients, serves promising tool guide decisions, including targeted therapy selection immunotherapy prediction, ultimately offering potential more personalized management

Language: Английский

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Targeting tumor-associated macrophages in colon cancer: mechanisms and therapeutic strategies

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

Published: March 21, 2025

Colon cancer (CC) remains a primary contributor to cancer-related fatalities worldwide, driven by difficulties in early diagnosis and constrained therapeutic options. Recent studies underscore the importance of tumor microenvironment (TME), notably tumor-associated macrophages (TAMs), fostering malignancy progression therapy resistance. Through their inherent plasticity, TAMs facilitate immunosuppression, angiogenic processes, metastatic spread, drug tolerance. In contrast M1 macrophages, which promote inflammatory tumoricidal responses, M2 support expansion dissemination exerting immunosuppressive pro-angiogenic influences. Consequently, manipulating has emerged as potential avenue enhance treatment effectiveness. This review outlines origins, polarization states, functions CC, highlights role driving advancement, surveys ongoing efforts target these cells for better patient outcomes. Emerging strategies aimed at modulating TAM - including depletion strategies, reprogramming approaches that shift M2-polarized toward an phenotype, inhibition key signaling pathways sustaining TAM-mediated immunosuppression-are currently under active investigation. These hold promise overcoming induced resistance improving immunotherapeutic efficacy CC.

Language: Английский

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Integrating multi-omics and machine learning methods reveals the metabolism of amino acids and derivatives-related signature in colorectal cancer

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

Published: March 26, 2025

Objective The metabolism of amino acids and derivatives (MAAD) is closely related to the occurrence development colorectal cancer (CRC), but specific regulatory mechanisms are not yet clear. This study aims explore role MAAD in progression ultimately identify key molecules that may become potential therapeutic targets for CRC. Methods integrates bulk transcriptome single-cell analyze MAAD-related genes from multiple levels. Subsequently, numerous machine learning methods were incorporated construct prognostic models, infiltration immune cells, tumor heterogeneity, mutation burden, pathway changes under different modes analyzed. Finally, identified experimental validation. Results We successfully constructed models Nomograms based on molecules. There was a notable survival benefit observed low-risk patients when contrasted with their high-risk counterparts. In addition, group had poorer response immunotherapy stronger heterogeneity compared group. Further research found by knocking down gene. LSM8, malignant characteristics cell lines significantly alleviated, suggesting LSM8 target. Conclusion gene likely involved CRC could be hopeful target intervention.

Language: Английский

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Molecular mechanisms and signaling pathways related to brain metastasis in breast cancer

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

Published: March 27, 2025

Brain metastasis in breast cancer (BCBM) significantly threatens the survival and quality of life patients, particularly those with triple-negative (TNBC) HER2-positive subtypes. It involves complex molecular mechanisms diverse signaling pathways. This review highlights recent research on pathways BCBM. The process BCBM includes several key steps: local infiltration cells into bloodstream subsequent spread to brain. They must then overcome blood-brain barrier (BBB) establish grow Multiple pathways, including PI3K/AKT, STAT3, NF-κB, Notch, Wnt are involved this process. Overall, is a disease regulated by multiple To improve patient life, it crucial deepen explore new treatment targets strategies. will enhance our understanding lead more effective treatments.

Language: Английский

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