Prognostic value of body adipose tissue parameters in cancer patients treated with immune checkpoint inhibitors

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

Published: Feb. 12, 2025

Objective This study aims to explore the relationship between body adipose tissue characteristics and clinical outcomes in cancer patients receiving immune checkpoint inhibitor (ICI) therapy. Methods We conducted an extensive literature search across three major online databases—Embase, PubMed, Cochrane Library—to identify studies examining link treatment undergoing ICI therapy, from inception of each database until February 20, 2024. The quality included was evaluated using Newcastle-Ottawa Scale. primary analyzed were hazard ratios (HRs) for overall survival (OS) progression-free (PFS), as well odds (ORs) disease control rate (DCR). Pooled estimates 95% confidence intervals (CIs) calculated. Results A total 23 included, encompassing 2741 patients. analysis revealed that with higher levels visceral (VAT) exhibited significantly improved OS (HR: 0.72, CI: 0.59–0.89, p < 0.001) PFS 0.80, 0.67–0.96, = 0.015), along a DCR (OR: 1.81, 1.26–2.60, 0.001), compared those lower VAT levels. Additionally, increased subcutaneous (SAT) associated better 0.69, 0.58–0.82, 0.82, 0.68–1.00, 0.049), 1.99, 1.15–3.44, 0.014). Elevated (TAT) also linked longer 0.73, 0.55–0.97, 0.028). However, visceral-to-subcutaneous ratio (VSR) shorter 1.43, 1.09–1.87, 0.010). No significant found TAT 0.81, 0.54–1.23, 0.332) VSR 1.20, 0.95–1.51, 0.131) ICI-treated Conclusion highlights prognostic relevance SAT predicting response ICIs. These findings suggest assessments should be incorporated into evaluations this patient population.

Language: Английский

---

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

---

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

---

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

---

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

---

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

---

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

---

Association between ethylene oxide exposure and serum sex hormone levels measured in a reference sample of the US general population

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

Published: April 11, 2025

Ethylene oxide (EO) is a crucial organic compound commonly utilized in industrial and medical products. Food Drug Administration (FDA)-approved EO sterilization sterilizes about 50% of sterile devices the U.S. Animal human studies have suggested that exposure may result severe health problem. However, evaluating relationship between sex hormones populations are still lacking. Therefore, further investigation into EO’s effects on humans essential. This cross-sectional study within National Health Nutrition Examination Survey (NHANES),2013–2016 examined EO-hemoglobin adducts (HbEO) hormones. HbEO was found to be inversely associated with estradiol (E2) positively ratio total testosterone (TT) E2 hormone-binding globulin (SHBG) levels adult males. Such associations SHBG were non-linear male adults. no significant steroids across various age groups females all except for Thus, our provides evidence potentially serve as an endocrine disruptor environment, affecting

Language: Английский

---

Exploring the link between serum uric acid and endometriosis: a cross-sectional analysis utilizing NHANES data from 1999-2006

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

Published: April 15, 2025

Substantial impacts on the female reproductive system have been definitively linked to heightened levels of serum uric acid. However, evidence directly linking increased acid endometriosis in women remains sparse, and precise characteristics this influence are still not fully understood. To explore exact relationship between endometriosis. Referencing data accumulated from National Health Nutrition Examination Survey (NHANES), study covers period 1999 2006, conducted an analysis 5,162 participants aged 20 54 years (representing a sample size approximately 66,927,890 women). The adopted cross-sectional methodology delve into tie prevalence Utilizing rigorous methodologies, including weighted multivariable logistic regression models, subgroup analyses, statistical methodologies for smooth curve fitting. A positive association was found continuous risk (OR = 1.25, 95% CI [1.09, 1.44], P 0.003). At same time, highest quartile had 133% higher compared with lowest (OR=2.33,95%CI [1.28, 4.23], P=0.009). fitting also linear correlation There no heterogeneity analysis. indicates strong link appearance women. Specifically, elevated face likelihood developing

Language: Английский

---

Age-period-cohort analysis of autism spectrum disorders-related prevalence and DALYs: based on the Global Burden Of Disease Study 2021

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

Published: April 25, 2025

The Sustainable Development Goals (SDGs) call for systematic monitoring to optimize child development outcomes. As a developmental disorder affecting children and adults, Autism Spectrum Disorder (ASD) not only impacts individual social functioning but also places burden on families society. A detailed analysis of the latest global data ASD can assist stakeholders in formulating support policies interventions, thereby helping meet health needs ASD. We used from Global Burden Disease Study 2021 (GBD 2021), compiled by Institute Health Metrics Evaluation (IHME). Data were obtained through Exchange (GHDx) covered 204 countries territories 1990 2019. Variables included ASD-related prevalence, mortality, disability-adjusted life years (DALYs), age-standardized rates, sociodemographic index (SDI). Exposure autism spectrum disorders contributed 61823540 prevalence 11544038 DALYs globally 2021. Males younger adults high-risk populations. Higher socio-demographic (SDI) regions areas. disease varied considerably across GBD countries. From 2021, number cases increased. predicted results showed that both genders would still increase 2022 2046. Countries or with higher SDI have greater improvement potential. has shown continuous upward trend, some differences observed gender, age groups, regions. In terms among females may be underestimated. Regarding aging process highlighted urgent need address elderly population. High-SDI should place emphasis improving diagnostic methods implementing precise while middle- low-SDI focus raising public awareness enhancing screening capabilities.

Language: Английский

---