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Clinical Epigenetics Jun 2024Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores...
BACKGROUND
Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is overrepresented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins.
RESULTS
In total, 104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjusted p-value < 8.3 × 10). These included EpiScores for chemokines, growth factors, proteins involved in neurogenesis and vascular development, cell membrane proteins and receptors, and other immune proteins. Three EpiScores were associated with SES, or the interaction between birth GA and SES: afamin, intercellular adhesion molecule 5, and hepatocyte growth factor-like protein (standardised estimates |0.06 to 0.13|, Bonferroni-adjusted p-value < 8.3 × 10). In a preterm subgroup (n = 217, median [range] GA 29.29 weeks [22.14 to 33.0 weeks]), SES-EpiScore associations did not remain statistically significant after adjustment for sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, and histological chorioamnionitis.
CONCLUSIONS
Low birth GA is substantially associated with a set of EpiScores. The set was enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. SES had fewer associations with EpiScores; these tended to have small effect sizes and were not statistically significant after adjusting for inflammatory comorbidities. This suggests that inflammation is unlikely to be the primary axis through which SES becomes embedded in the development of preterm infants in the neonatal period.
Topics: Humans; Saliva; Female; Infant, Newborn; Gestational Age; Epigenesis, Genetic; Male; DNA Methylation; Premature Birth; Pregnancy; Infant, Premature; Social Class; Adult; Inflammation
PubMed: 38951914
DOI: 10.1186/s13148-024-01701-2 -
Functional & Integrative Genomics Jun 2024The gene C5orf34 exhibits evolutionary conservation among mammals, and emerging evidence suggests its potential involvement in tumor development; however, comprehensive...
The gene C5orf34 exhibits evolutionary conservation among mammals, and emerging evidence suggests its potential involvement in tumor development; however, comprehensive investigations of this gene are lacking. This study aims to elucidate the functional attributes and underlying mechanisms of C5orf34 in cancer. To evaluate its clinical predictive value, we conducted an analysis of the pan-cancerous expression, clinical data, mutation, and methylation data of C5orf34. Additionally, we investigated the correlation between C5orf34 and tumor mutant load (TMB), immune cell infiltration, and microsatellite instability (MSI) through relevant analyses. Furthermore, immunohistochemical (IHC) staining was employed to validate clinical samples, while knockdown and overexpression experiments and transcriptome RNA sequencing were utilized to examine the impact of C5orf34 on LUAD cells. According to our study, C5orf34 exhibits high expression levels in the majority of malignant tumors. The upregulation of C5orf34 is governed by DNA copy number alterations and methylation patterns, and it is closely associated with patients' survival prognosis and immune characteristics, thereby holding significant clinical implications. Furthermore, IHC staining analysis, cellular experiments, and transcriptome RNA sequencing have provided evidence supporting the role of C5orf34 in modulating the cell cycle to promote LUAD proliferation, migration, and invasion. This highlights its potential as a promising therapeutic target. The findings of this investigation suggest that C5orf34 may serve as a valuable biomarker for various tumor types and represent a potential target for immunotherapy, particularly in relation to the proliferation, migration, and apoptosis of LUAD cells.
Topics: Humans; Lung Neoplasms; Cell Proliferation; DNA Methylation; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Prognosis; DNA Copy Number Variations; Cell Movement; Biomarkers, Tumor; Microsatellite Instability; Mutation
PubMed: 38951221
DOI: 10.1007/s10142-024-01397-w -
Zhonghua Fu Chan Ke Za Zhi Jun 2024To investigate the effect of DNA methylation of laminin α3 (LAMA3) on the prognosis of platinum-resistant epithelial ovarian cancer (EOC) and its possible mechanism....
To investigate the effect of DNA methylation of laminin α3 (LAMA3) on the prognosis of platinum-resistant epithelial ovarian cancer (EOC) and its possible mechanism. (1) The relationship between DNA methylation of LAMA3 and platinum resistance in EOC was evaluated by bioinformatics. (2) A total of 67 EOC patients treated at Guangxi Medical University Cancer Hospital from January 2000 to December 2012 were selected to detect the levels of LAMA3 DNA methylation in EOC tissues using pyrophosphate sequencing technology to explore its diagnostic efficacy for platinum resistance and prognosis in EOC patients. Furthermore, its impact on chemotherapy efficacy and prognosis of platinum resistant EOC patients were also analyzed. (1) Ten proteins highly interacting with LAMA3 were screened from the Gene Interaction Retrieval Platform (STRING) database, including laminin β (LAMB) 3, laminin γ (LAMC) 3, integrin α (ITGA) 6, intestine protein β4 (ITGB4), ITGA3, LAMC1,LAMB2, dystrophin associated glycoprotein 1 (DAG1), LAMB1 and cytochrome P450c17α (COL17A1) protein; kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that LAMA3 and its related interacting proteins participate in the regulation of malignant tumor occurrence and development through signaling pathways such as apoptosis, cell cycle, DNA damage response, epithelial mesenchymal transition (EMT), androgen receptor (AR), estrogen receptor (ER), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt), RAS/mitogen activated protein kinase (MAPK), receptor tyrosine kinase (RTK), tuberous sclerosis protein complex (TSC)/mammalian target of rapamycin (mTOR), and their expression levels were related to the sensitivity of chemotherapy drugs such as cisplatin in EOC. (2) Our clinical data analysis found that the LAMA3 DNA methylation level in EOC tissue of the platinum-sensitive group (35 cases) was 71% (25/35), which was higher than 69% (22/32) in the platinum-resistant group (32 cases), with statistically insignificant difference (=0.057, =0.811). The area under the curve (AUC) of LAMA3 DNA methylation level for assessing platinum resistance in EOC was 0.601, and the AUC for predicting EOC patient prognosis was 0.686. The chemotherapy efficacy of EOC patients with high methylation of LAMA3 DNA was worse than that of patients with low methylation, 50% (12/24) vs 15/15, with statistically significant difference (=10.833, =0.001). The level of LAMA3 DNA methylation had a significant impact on the progression free survival and overall survival of EOC patients (both <0.05). The level of LAMA3 DNA methylation has certain diagnostic and predictive value for platinum resistance and prognosis in EOC patients, which may be closely related to the regulatory mechanism, platinum resistance and prognosis of EOC.
Topics: Humans; Female; Laminin; DNA Methylation; Drug Resistance, Neoplasm; Computational Biology; Carcinoma, Ovarian Epithelial; Prognosis; Ovarian Neoplasms; Gene Expression Regulation, Neoplastic; Antineoplastic Agents; Platinum; Signal Transduction
PubMed: 38951081
DOI: 10.3760/cma.j.cn112141-20240201-00069 -
Environmental Pollution (Barking, Essex... Jun 2024Associations between indoor air pollution from fine particulate matter (PM with aerodynamic diameter d < 2.5 μm) and human health are poorly understood. Here, we...
Associations between fine particulate matter, gene expression, and promoter methylation in human bronchial epithelial cells exposed within a classroom under Air-Liquid Interface.
Associations between indoor air pollution from fine particulate matter (PM with aerodynamic diameter d < 2.5 μm) and human health are poorly understood. Here, we analyse the concentration-response curves for fine and ultrafine PM, the gene expression, and the methylation patterns in human bronchial epithelial cells (BEAS-2B) exposed at the air-liquid interface (ALI) within a classroom in downtown Rome. Our results document the upregulation of aryl hydrocarbon receptor (AhR) and genes associated with xenobiotic metabolism (CYP1A1 and CYP1B1) in response to single exposure of cells to fresh urban aerosols at low fine PM mass concentrations within the classroom. This is evidenced by concentrations of ultrafine particles (UFPs, dp < 0.1 μm), polycyclic aromatic hydrocarbons (PAH), and ratios of black carbon (BC) to organic aerosol (OA). Additionally, an interleukin 18 (IL-18) down-regulation was found during periods of high human occupancy. Despite the observed gene expression dysregulation, no changes were detected in the methylation levels of the promoter regions of these genes, indicating that the altered gene expression is not linked to changes in DNA methylation and suggesting the involvement of another epigenetic mechanism in the gene regulation. Gene expression changes at low exposure doses have been previously reported. Here, we add the possibility that lung epithelial cells, when singly exposed to real environmental concentrations of fine PM that translate into ultra-low doses of treatment, may undergo epigenetic alteration in the expression of genes related to xenobiotic metabolism. Our findings provide a perspective for future indoor air quality regulations. We underscore the potential role of indoor UFPs as carriers of toxic molecules with low-pressure weather conditions, when rainfall and strong winds may favour low levels of fine PM.
PubMed: 38950846
DOI: 10.1016/j.envpol.2024.124471 -
Nutrition and Cancer Jul 2024The resistance of colorectal cancer (CRC) to conventional therapeutic modalities, such as radiation therapy and chemotherapy, along with the associated side effects,... (Review)
Review
The resistance of colorectal cancer (CRC) to conventional therapeutic modalities, such as radiation therapy and chemotherapy, along with the associated side effects, significantly limits effective anticancer strategies. Numerous epigenetic investigations have unveiled that naturally occurring stilbenes can modify or reverse abnormal epigenetic alterations, particularly aberrant DNA methylation status, offering potential avenues for preventing or treating CRC. By modulating the activity of the DNA methylation machinery components, phytochemicals may influence the various stages of CRC carcinogenesis through multiple molecular mechanisms. Several epigenetic studies, especially preclinical research, have highlighted the effective DNA methylation modulatory effects of stilbenes with minimal adverse effects on organisms, particularly in combination therapies for CRC. However, the available preclinical and clinical data regarding the effects of commonly encountered stilbenes against CRC are currently limited. Therefore, additional epigenetic research is warranted to explore the preventive potential of these phytochemicals in CRC development and to validate their therapeutic application in the prevention and treatment of CRC. This review aims to provide an overview of selected bioactive stilbenes as potential chemopreventive agents for CRC with a focus on their modulatory mechanisms of action, especially in targeting alterations in DNA methylation machinery in CRC.
PubMed: 38950568
DOI: 10.1080/01635581.2024.2364391 -
ACS Biomaterials Science & Engineering Jul 2024Early detection of cancer is vital for increasing patient survivability chances. The three major techniques used to diagnose cancers are instrumental examination, tissue... (Review)
Review
Early detection of cancer is vital for increasing patient survivability chances. The three major techniques used to diagnose cancers are instrumental examination, tissue biopsy, and tumor biomarker detection. Circulating tumor DNA (ctDNA) has gained much attention in recent years due to advantages over traditional technology, such as high sensitivity, high specificity, and noninvasive nature. Through the mechanism of apoptosis, necrosis, and circulating exosome release in tumor cells, ctDNA can spread throughout the circulatory system and carry modifications such as methylations, mutations, gene rearrangements, and microsatellite instability. Traditional gene-detection technology struggles to achieve real-time, low-cost, and portable ctDNA measurement, whereas electrochemical biosensors offer low cost, high specificity alongside sensitivity, and portability for the detection of ctDNA. Therefore, this review focuses on describing the recent advancements in ctDNA biomarkers for various cancer types and biosensor developments for real-time, noninvasive, and rapid ctDNA detection. Further in the review, ctDNA sensors are also discussed in regards to their selections of probes for receptors based on the electrode surface recognition elements.
PubMed: 38950521
DOI: 10.1021/acsbiomaterials.4c00606 -
Oncology Nursing Forum Jun 2024To explore genes in the nuclear factor E2-related factor 2 antioxidative response elements (Nrf2-ARE) signaling pathway using a multiomics approach for associations with...
Association Between Genes in the Nuclear Factor E2-Related Factor 2 Antioxidative Response Elements Pathway and Cancer-Related Fatigue in Women With Early-Stage Breast Cancer.
OBJECTIVES
To explore genes in the nuclear factor E2-related factor 2 antioxidative response elements (Nrf2-ARE) signaling pathway using a multiomics approach for associations with variability of cancer-related fatigue (CRF) in postmenopausal women with early-stage hormone receptor-positive breast cancer.
SAMPLE & SETTING
Postmenopausal women (N = 116) with early-stage hormone receptor-positive breast cancer were recruited from western Pennsylvania.
METHODS & VARIABLES
Candidate genes from the Nrf2-ARE pathway were investigated for associations with CRF occurrence and severity. Associations were evaluated using logistic regression for occurrence and linear regression for severity.
RESULTS
The rs2706110 TT genotype in NFE2L2 was associated with a 3.5-fold increase in odds of CRF occurrence. The cytosine-phosphate-guanine (CpG) site cg22820568 in PRDX1 was associated with CRF occurrence and severity.
IMPLICATIONS FOR NURSING
Biomarkers based on Nrf2-ARE genes may help to identify women at increased risk for more severe CRF and to develop targeted interventions.
Topics: Humans; Female; Breast Neoplasms; NF-E2-Related Factor 2; Fatigue; Middle Aged; Aged; Antioxidant Response Elements; Signal Transduction; Postmenopause; Pennsylvania; Neoplasm Staging
PubMed: 38950096
DOI: 10.1188/24.ONF.404-416 -
Oncology Nursing Forum Jun 2024To determine associations among DNA methylation of brain-derived neurotrophic factor (BDNF) and RAS p21 protein activator 2 (RASA2) genes with processing speed and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To determine associations among DNA methylation of brain-derived neurotrophic factor (BDNF) and RAS p21 protein activator 2 (RASA2) genes with processing speed and perceived cognitive function.
SAMPLE & SETTING
This was a cross-sectional, secondary analysis of baseline data from a randomized controlled trial, the Exercise Program in Cancer and Cognition Study.
METHODS & VARIABLES
Data included M values for DNA methylation of the BDNF and RASA2 genes; processing speed, objectively measured using the Grooved Pegboard and Digit Vigilance Test scores; and perceived cognitive function, self-reported using the Patient Assessment of Own Functioning Inventory. Regression analysis was conducted.
RESULTS
Greater methylation of cg21291635 of the BDNF gene (p = 0.01) and cg20247102 of the RASA2 gene (p = 0.013) were associated with poorer processing speed, whereas greater methylation of cg20108357 of the BDNF gene (p < 0.001) and cg00567892 of the RASA2 gene (p = 0.019) were associated with better perceived cognitive function.
IMPLICATIONS FOR NURSING
Gene methylation variations were demonstrated, suggesting the genes' potential roles and two possible distinct mechanisms of cognitive function in cancer. .
Topics: Humans; Brain-Derived Neurotrophic Factor; Female; DNA Methylation; Middle Aged; Cross-Sectional Studies; Breast Neoplasms; Aged; Postmenopause; Cognition
PubMed: 38950092
DOI: 10.1188/24.ONF.349-360 -
Addiction Biology Jul 2024Opioid use disorder (OUD) is a multifaceted condition influenced by sex, genetic and environmental factors that could be linked with epigenetic changes. Understanding...
Opioid use disorder (OUD) is a multifaceted condition influenced by sex, genetic and environmental factors that could be linked with epigenetic changes. Understanding how these factors interact is crucial to understand and address the development and progression of this disorder. Our aim was to elucidate different potential epigenetic and genetic mechanisms between women and men that correlate with OUD under real-world pain unit conditions. Associations between analgesic response and the DNA methylation level of the opioid mu receptor (OPRM1) gene (CpG sites 1-5 selected in the promoter region) were evaluated in 345 long opioid-treated chronic non cancer pain: cases with OUD (n = 67) and controls (without OUD, n = 278). Cases showed younger ages, low employment status and quality of life, but higher morphine equivalent daily dose and psychotropic use, compared to the controls. The patients with OUD showed a significant decrease in OPRM1 DNA methylation, which correlated with clinical outcomes like pain relief, depression and different adverse events. Significant differences were found at the five CpG sites studied for men, and exclusively in women for CpG site 3, in relation to OUD diagnosis. These findings support the importance of epigenetics and sex as biological variables to be considered toward efficient OUD understanding and therapy development.
Topics: Humans; Receptors, Opioid, mu; DNA Methylation; Male; Female; Epigenesis, Genetic; Chronic Pain; Opioid-Related Disorders; Middle Aged; Adult; Sex Factors; Analgesics, Opioid; Case-Control Studies; CpG Islands; Quality of Life
PubMed: 38949208
DOI: 10.1111/adb.13422 -
Medicine and Science in Sports and... Jul 2024Epigenetic aging, a marker of biological aging measured by DNA methylation, may be affected by behaviors, including sleep and physical activity. However, investigations...
INTRODUCTION
Epigenetic aging, a marker of biological aging measured by DNA methylation, may be affected by behaviors, including sleep and physical activity. However, investigations of physical activity and sleep with epigenetic aging among pediatric populations are scant and have not accounted for correlated behaviors.
METHODS
The study population included 472 Mexico City adolescents (52% female). Blood collection and 7-day wrist actigraphy (Actigraph GTX-BT) occurred during a follow-up visit when participants were 14.5 (2.09) years. Leukocyte DNA methylation was measured with the Infinium MethylationEPIC array after bisulfite conversion, and 9 epigenetic clocks were calculated. Sleep vs wake time was identified through a pruned dynamic programing algorithm, and physical activity was processed with Chandler cut-offs. Kmeans clustering was used to select actigraphy-assessed physical activity and sleep behavior clusters. Linear regression analyses were used to evaluate adjusted associations between the clusters and epigenetic aging.
RESULTS
There were 3 unique clusters: "Short sleep/high sedentary behavior", "Adequate sleep duration and late timing/low moderate or vigorous physical activity (MVPA)", and "Adequate sleep duration/high MVPA". Compared to the "Adequate duration/high MVPA", adolescents with "Adequate duration and late sleep timing/low MVPA" had more accelerated aging for the GrimAge clock (β = 0.63;95% CI 0.07, 1.19). In pubertal-stratified analyses, more mature adolescents in the "Adequate duration and late sleep timing/low MVPA group" had accelerated epigenetic aging. In contrast, females in the "Short sleep/high sedentary" group had decelerated epigenetic aging for the Wu pediatric clock.
CONCLUSIONS
Associations between behavior clusters and epigenetic aging varied by pubertal status and sex. Contrary results in the Wu clock suggest the need for future research on pediatric-specific clocks.
PubMed: 38949160
DOI: 10.1249/MSS.0000000000003498