Causal relationship between immune cell phenotypes and risk of biliary tract cancer: evidence from Mendelian randomization analysis

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

Published: July 10, 2024

Biliary tract cancer stands as a prevalent illness, posing significant risks to human health, where immune cells are pivotal in both its development and recovery processes. Due the diverse functionalities exhibited by different cell phenotypes within organism, relatively limited research on their relationship with biliary cancer, this study employed Mendelian randomization (MR) explore potential association, thereby aiding better understanding of causal link between cancer.

Language: Английский

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New insights into the mechanisms of the immune microenvironment and immunotherapy in osteosarcoma

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

Published: Jan. 17, 2025

Osteosarcoma, a malignant bone tumor primarily affecting adolescents, is highly invasive with poor prognosis. While surgery and chemotherapy have improved survival for localized cases, pulmonary metastasis significantly reduces to approximately 20%, highlighting the need novel treatments. Immunotherapy, which leverages immune system target osteosarcoma cells, shows promise. This review summarizes biological characteristics of osteosarcoma, mechanisms metastasis, microenvironment (TME). It involves recent immunotherapy advances, including monoclonal antibodies, vaccines, cell therapies, checkpoint inhibitors, oncolytic viruses, discusses combining these standard

Language: Английский

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Causal relationship between immune cells and risk of heart failure: evidence from a Mendelian randomization study

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 23, 2025

Background Heart failure (HF) is a clinical syndrome resulting from structural damage or dysfunction of the heart. Previous investigations have highlighted critical involvement immune cells in progression heart failure, with distinct roles attributed to different types cells. The objective current research was explore potential connections between characteristics and development HF, as well ascertain nature causality these factors. Methods To assess causal association immunological profiles HF based on publicly available genome-wide studies, we employed two-sample Mendelian randomization technique, utilizing inverse variance weighted (IVW) method our primary analytical approach. In addition, assessed heterogeneity cross-sectional pleiotropy through sensitivity analyses. Results A (MR) analysis conducted using IVW method. At significance level 0.001, identified 40 immunophenotypes that significant relationship HF. There phenotypes failure. These immunophenotypes, 8 which were B cells, 5 cDC, 2 T cell maturation stage, monocytes, 3 myeloid 7 TBNK 13 Treg. Sensitivity analyses validate strength reliability MR findings. Conclusions Our study suggests there appears be effect multiple This discovery provides new avenue for therapeutic treatments target drug development.

Language: Английский

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Causal Associations Between Immune Cell Phenotypes and Varicose Veins: A Mendelian Randomization Analysis

Annals of Vascular Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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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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Circulating cell-free DNA methylation analysis of pancreatic cancer patients for early noninvasive diagnosis

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

Published: March 10, 2025

Background Aberrant hypermethylation of genomic DNA CpG islands (CGIs) is frequently observed in human pancreatic cancer (PAC). A plasma cell-free (cfDNA) methylation analysis method can be utilized for the early and noninvasive detection PAC. This study also aimed to differentiate PAC from other types. Methods We employed methylated tandem amplification sequencing (MCTA-Seq) method, which targets approximately one-third CGIs, on samples patients (n = 50) healthy controls 52), as well cancerous adjacent noncancerous tissue 66). The method’s efficacy detecting distinguishing it hepatocellular carcinoma (HCC), colorectal (CRC), gastric (GC) was evaluated. Additionally, a score typing system established. Results identified total 120 cfDNA biomarkers, including IRX4 , KCNS2 RIMS4 blood. panel comprising these biomarkers achieved sensitivity 97% 86% discovery validation cohorts, respectively, with specificity 100% both cohorts. scoring systems were clinically applicable. Furthermore, we hundreds differentially between HCC, CRC, GC. Certain combinations markers used highly specific (approximately 100%) algorithm GC Conclusions Our PAC, offering novel approach early, diagnosis

Language: Английский

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Cholangiocarcinoma: The era of liquid biopsy

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(11)

Published: March 12, 2025

Cholangiocarcinoma (CCA) is a highly aggressive and heterogeneous malignancy arising from the epithelial cells of biliary tract. The limitations current methods in diagnosis CCA highlight urgent need for new, accurate tools early cancer detection, better prognostication patient monitoring. Liquid biopsy (LB) modern non-invasive technique comprising diverse group methodologies aiming to detect tumour biomarkers body fluids. These include circulating cells, cell-free DNA, RNA extracellular vesicles. aim this review explore potential future applications LB management, with focus on diagnosis, We examine both its significant inevitable associated technology. conclude that holds considerable promise, but further research necessary fully integrate it into precision oncology CCA.

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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Causal relationship between immune cells and risk of myocardial infarction: evidence from a Mendelian randomization study

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 27, 2024

Background Atherosclerotic plaque rupture is a major cause of heart attack. Previous studies have shown that immune cells are involved in the development atherosclerosis, but different play roles. The aim this study was to investigate causal relationship between immunological traits and myocardial infarction (MI). Methods To assess association profiles with based on publicly available genome-wide studies, we used two-sample mendelian randomization (MR) approach inverse variance weighted (IVW) as main analytical method. Sensitivity analyses were heterogeneity horizontal pleiotropy. Results A MR analysis conducted using IVW primary At significance level 0.001, identified 47 immunophenotypes significant MI. Seven these present B cells, five cDC, four T at maturation stage, six monocytes, myeloid 12 TBNK eight Treg cells. performed confirm robustness results. Conclusions Our results provide strong evidence multiple effect risk infarction. This discovery provides new avenue for therapeutic treatments target drug development.

Language: Английский

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