Colorectal cancer (CRC) is the third most prevalent cancer and one of the leading causes of cancer-related mortality in the world. Early detection is crucial in preventing deaths, but current screening methods have various limitations. So today, much attention is focused on genetic changes, including mutations in oncogenes and tumor suppressor genes, and epigenetic modifications such as aberrant methylation and alterations in the expression of specific microRNAs that contribute to CRC development. This has led to the discovery of more specific and sensitive molecular biomarkers. Furthermore, the use of liquid biopsy, which has a high potential for identifying molecular tumor markers, provides a perspective for overcoming the limitations of conventional screening methods. In this review, we first discuss the intricate molecular processes involved in the development of colorectal tumors. We then delve into the concept of liquid biopsy, exploring its traceable components such as extracellular vesicles, circulating tumor cells, circulating tumor DNAs, and circulating tumor RNAs. We also examine various methods for analyzing these components to identify molecular biomarkers for CRC screening. Additionally, we refer to the development of new diagnostic kits for CRC, such as Epi proColon, ColoSure, and Cologuard, which offer non-invasive utilization of genetic and epigenetic biomarkers. Lastly, we address the current challenges faced in using these biomarkers in a clinical setting. Despite the obstacles, these non-invasive and reliable markers have the potential to enable early detection of CRC and likely increase screening uptake, potentially replacing current modalities.

Background: Treatment-resistant depression (TRD) affects up to 30–40% of patients with major depressive disorder and remains a major therapeutic challenge. Genetic and epigenetic factors are increasingly recognized as key contributors to both vulnerability and treatment response. Methods: We conducted a narrative review of studies published between 2021 and 2025, focusing exclusively on DNA- and RNA-based biomarkers of TRD. Twelve studies met the inclusion criteria, covering candidate gene analyses, genome-wide association studies (GWAS), neuroimaging–genetic approaches, and microRNA profiling. Results: Genetic investigations consistently implicate neuroplasticity-related genes (BDNF, NTRK2, PTEN, SYN1, MAPK1, and GSK3B) in the risk of TRD and its relapse. Variants in glutamatergic receptor genes (GRIN2A, GRIN2B, GRIA2, GRIA3) were predicted to result in a rapid and sustained response to ketamine. Genomic approaches further demonstrated that composite genetic panels outperform single-variant predictors. In parallel, microRNAs such as miR-1202, miR-16, miR-135, miR-124, miR-223, and miR-146a emerged as dynamic biomarkers of treatment response, particularly in cohorts treated with ketamine or electroconvulsive therapy. Conclusions: DNA- and RNA-based biomarkers provide promising avenues for improving the understanding and management of TRD. Their integration into clinical frameworks could support patient stratification, individualized treatment selection, and real-time monitoring of therapeutic efficacy. Future research should prioritize replication, methodological harmonization, and longitudinal validation to facilitate the translation of findings into precision psychiatry.

Flow cytometry studies have reported an association between lower regulatory T cells (Treg) in cord blood and subsequent food allergy. Flow cytometry, however, is a resource-intensive technique. We therefore aimed to develop an epigenetic biomarker (nTregepi) that correlates with the proportion of naïve regulatory T cells (nTreg) in cord blood white cells (CBWCs) measured by flow cytometry. We then investigated the association between nTregepi and subsequent food allergy. The Barwon Infant Study (BIS) is a prebirth cohort study (n = 1074 infants). Illumina Infinium MethylationEPIC v1.0 BeadChips were used to assess DNA methylation in cord whole blood (n = 936). In a subgroup, flow cytometry was used to measure the proportion of nTregs (CD4 + CD45RA + FOXP3+) in CBWCs (n = 450). In a training set (n = 338), we assessed the correlation between methylation at 78 probes in the FOXP3 and TIGIT genes and the proportion of nTregs in CBWCs. LASSO regression was then used to develop a linear methylation predictor of nTregs as a proportion of CBWCs, denoted 'nTregepi', which was then tested in a validation set (n = 112). The association between nTregepi and subsequent IgE-mediated food allergy was evaluated using logistic regression. Methylation levels of 23/78 sites in FOXP3 and TIGIT were associated with the proportion of nTregs in CBWCs (q < 0.05 for each). LASSO regression of methylation levels for these 21 probes was used to derive a linear predictor (nTregepi) which correlated with the log proportion of nTregs in the validation set (R2 = 0.22, p < 0.001). In the complete cohort with relevant data available (n = 693), a higher nTregepi was associated with decreased odds of food allergy (odds ratio 0.65 (95% CI 0.48-0.88, p = 0.005)). A composite epigenetic biomarker in cord whole blood correlates with the proportion of nTreg in CBWCs and is strongly associated with the absence of subsequent food allergy.

Novel epigenetic biomarkers following ferroptosis and pyroptosis in a hypobaric hypoxia-induced renal injury model.

Lactylation and methylation: Dual epigenetic codes and potential therapeutic targets in myocardial aging.

Synergistic transgenerational reproductive toxicity of polystyrene nanoplastics and butylparaben at NOAEL levels via SET-2-mediated H3K4me3 modification in Caenorhabditis elegans.

Developmental timing of index trauma exposure and accelerated epigenetic aging in United States military veterans.

Epigenetic effects of cadmium and lead in asthma: Cadmium-specific associations with ADRB2 methylation and miRNA-146a expression in Egyptian Adults.

Hepatocellular carcinoma (HCC) development in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern, but the underlying mechanisms are not fully understood. Epigenetic aging biomarkers, reflecting cellular and tissue aging, have been linked to various age-related pathologies, but their association with MASLD-HCC is unknown. We investigated associations between five epigenetic aging biomarkers and MASLD-HCC risk. We performed whole blood DNA methylation assay (Infinium 850k array) and calculated principal components-based (PC) versions of HorvathAge, HannumAge, PhenoAge and GrimAge and the DunedinPACE aging rate. We further calculated relative age accelerations for PCHorvathAge, PCHannumAge, PCPhenoAge and PCGrimAge. The aging biomarkers were modelled as continuous variables and categorised into tertiles based on distributions among controls. Associations between each aging biomarker and MASLD-HCC were examined using logistic regression, calculating odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for covariates. Data on 272 MASLD-HCC cases and 316 cancer-free MASLD controls recruited from six sites and matched on chronological age, sex and study site were analysed. Higher relative age accelerations of PCPhenoAge (ORT3 vs. T1 = 2.25, 95% CI: 1.45-3.50; ORcontinuous = 1.04, 95% CI: 1.02-1.07, p = 0.009), PCGrimAge (ORT3 vs. T1 = 3.97, 95% CI: 2.41-6.64; ORcontinuous = 1.16, 95% CI: 1.10-1.24, p = 8.76 × 10-07) and DunedinPACE (ORT3 vs. T1 = 3.45, 95% CI: 2.17-5.55; ORcontinuous = 1.72, 95% CI: 1.43-2.10, p = 2.58 × 10-08) were associated with MASLD-HCC, but not PCHorvathAge or PCHannumAge. Higher relative age accelerations of PCPhenoAge, PCGrimAge and DunedinPACE aging rate are associated with risk of MASLD-HCC. These aging biomarkers could improve HCC risk assessment and facilitate risk stratification in patients with MASLD.

Epigenetics encompasses heritable but reversible modifications of gene expression that occur without changes in the DNA sequence and involve mechanisms such as DNA and RNA methylation and histone modifications. These mechanisms modulate chromatin architecture, genome stability, and cellular responses to environmental stressors, and their dysregulation contributes to oncogenesis and cancer progression. In parallel, radiotherapy remains a cornerstone of cancer treatment; furthermore, ionizing radiation induces epigenetic modifications alongside direct DNA double-strand breaks and oxidative damage. Radiation-induced epigenetic changes, including global or locus-specific DNA methylation shifts (e.g., genes promoter CpG islets), histone acetylation and methylation imbalances, are increasingly recognized as key contributors to molecular radioresistance. These adaptive responses may enhance tumor cell survival, affect therapeutic efficacy, and promote metastasis. Understanding the interplay between radiation exposure and epigenetic remodeling opens new perspectives for precision oncology and diagnostics. Epigenetic biomarkers hold potential for predicting treatment response and prognosis, while epigenetic modifiers may sensitize tumors to radiation. This review summarizes current evidence on radiation-induced epigenetic mechanisms and evaluates their diagnostic, prognostic, and therapeutic implications in cancer management.

While DNA methylation (DNAm)-based algorithms of aging show promise for predicting age-related diseases, their comparative utility for incident cardiovascular disease (CVD) remains underexplored. We aimed to systematically compare 13 DNAm algorithms in relation to CVD risk in older adults. This prospective cohort study included 2112 participants from the US HRS (Health and Retirement Study) with baseline DNAm data (2016) and 6-year follow-up. DNAm profiling was performed using the Infinium MethylationEPIC BeadChip kit (EPIC, Illumina, San Diego, CA). Thirteen widely used DNAm algorithms of aging were evaluated. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs per 1-SD increase in risk scores for incident CVD, including any CVD, congestive heart failure, and stroke. During a median of 37 months' follow-up, a total of 288 CVD cases (congestive heart failure, 38; stroke, 152) were observed. Zhang_DNAmAge, methylation Pace of Aging, and DNAmGrimAgeAcc showed positive associations with any CVD risk, with HRs per SD increase of 1.25 (95% CI, 1.07-1.45), 1.16 (95% CI, 1.02-1.33), and 1.24 (95% CI, 1.05-1.47), respectively. For specific CVD subtypes, DNAmGrimAge was associated with congestive heart failure risk (HR, 1.47 [95% CI, 1.11-1.95]), while both mPoA (HR, 1.24 [95% CI, 1.03-1.49]) and HorvathAcc (HR, 1.28 [95% CI, 1.07-1.55]) predicted incident stroke. Significant dose-response relationships (P-trend <0.05) were observed for Zhang_DNAmAge and DNAmGrimAgeAcc across all CVD outcomes. Zhang_DNAmAge, methylation Pace of Aging, and DNAmGrimAgeAcc function as independent predictors of incident CVD. These epigenetic biomarkers may improve early CVD detection and risk stratification in aging populations.

Periodontitis and Alzheimer's disease (AD) are chronic disorders that share an underlying inflammatory component and emerging epigenetic mechanisms influencing disease progression. Alterations in DNA methylation are increasingly recognized as critical in modulating immune responses and neurodegenerative processes. This review examines the evidence linking periodontal inflammation to AD pathogenesis and evaluates the potential of blood-based epigenetic biomarkers for early diagnosis and risk stratification. A narrative review was conducted by integrating findings from both preclinical and clinical studies that investigated the relationship between periodontitis and AD. Emphasis was placed on research assessing DNA methylation profiles, gene expression alterations, and the impact of proinflammatory mediators on the central nervous system. Particular attention was given to studies examining the role of the immune and complement systems in mediating the effects of chronic oral inflammation. The evidence indicates that chronic periodontal inflammation can trigger systemic responses that compromise the integrity of the blood-brain barrier, thereby facilitating the accumulation of amyloid-β plaques and hyperphosphorylated tau proteins in the brain. Aberrant methylation patterns in genes related to immune regulation and protein processing suggest converging molecular pathways between periodontitis and AD. Moreover, emerging data reveal that epigenetic alterations detectable in peripheral blood closely mirror cerebral changes, opening new avenues for early detection. As a narrative review, our synthesis is hypothesis-generating and does not establish causality; the proposed epigenetic link between periodontitis and AD remains provisional pending longitudinal and interventional confirmation.

Type 1 diabetes (T1D) arises from autoimmune destruction of pancreatic β-cells, yet genetic predisposition alone cannot fully account for its onset. Environmental triggers and epigenetic regulation have emerged as contributors bridging external exposures with immune and metabolic dysfunction. This review synthesizes current evidence on three major non-genetic domains influencing T1D pathogenesis. The Environmental Triggers section focuses on vitamin D and enterovirus. Vitamin D is discussed for its potential role in immune tolerance, while enterovirus represents a well-supported infectious trigger associated with β-cell autoimmunity. The Epigenetic Regulation section highlights how epigenetic and multi-omics studies reveal and associate with biological mechanisms and T1D onset, via DNA methylation, histone modification, and non-coding RNA pathways. Collectively, these perspectives illustrate how environmental exposures can influence immune and transcriptional networks beyond genetic susceptibility. The review concludes by outlining future research priorities, including longitudinal multi-omics studies and the identification of modifiable epigenetic biomarkers, which may provide new insights in exploring disease mechanisms and foster the development of targeted prevention and therapeutic strategies for T1D.

Abstract Gastric cancer continues to be a major threat to global health, accounting for a significant number of cancer deaths annually, with precancerous lesions representing critical intervention windows to halt malignant progression. Current risk stratification for malignant transformation in gastric precancerous lesions relies heavily on invasive endoscopic and histopathological assessments, which lack precision in quantifying individual transformation risk. Recent research points to the significance of epigenetic dysregulation in driving the evolution of gastric precancerous lesions: DNA methylation, 5‐hydroxymethylcytosine, non‐coding RNAs, RNA editing and modifications. Integrating multi‐omics epigenetic signatures offers a transformative approach to refining risk stratification, guiding personalised surveillance intervals and therapeutic interventions. Future efforts should prioritise large‐scale clinical validation of epigenetic biomarkers, standardisation of detection technologies, and development of cost‐effective, non‐invasive platforms to bridge mechanistic insights into precision prevention strategies for gastric carcinogenesis.

Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (NEDHSIL), also known as MEF2C-related disorder or MEF2C haploinsufficiency syndrome (MCHS), is a condition caused by pathogenic variants in the Myocyte Enhancer Factor-2C (MEF2C) gene. This study aimed to identify a DNA methylation episignature specific to NEDHSIL and explore its similarities with other known episignatures. Genome-wide DNA levels were assessed in a cohort of patients with MEF2C mutations and controls, and differentially methylated CpG sites were identified. A bioinformatic analysis yielded a classifier that was trained against controls and other known episignature disorders within the EpiSign Knowledge Database. The classifier demonstrated high accuracy, sensitivity, and specificity in classifying NEDHSIL samples. Furthermore, functional annotation and comparative analysis revealed similarities between the NEDHSIL episignature and other genetic neurodevelopmental disorders. This study provides evidence for a DNA methylation episignature specific to NEDHSIL and highlights the potential utility of this epigenetic biomarker for diagnosing and understanding molecular pathophysiology of neurodevelopmental disorders associated with MEF2C mutations.

Abstract Cancer is among the most prevalent diseases worldwide and a leading cause of death. Although histopathological analysis of tumor tissue obtained through biopsy remains the gold standard for diagnosis, liquid biopsy (LB) has emerged as a minimally invasive and promising alternative, enabling the detection and analysis of tumor-derived biomarkers in body fluids. This study focuses on the five most common global cancers: lung, breast, colorectal, prostate, and gastric cancers. Blood, plasma, and serum are the primary fluids analyzed, with biomarkers such as exosomes, microRNAs, circulating tumor cells (CTCs), and circulating tumor DNAs (ctDNAs) under investigation. Among these biomarkers, ctDNAs and CTCs show the greatest clinical relevance. LB offers applications in diagnosis, prognosis, treatment monitoring, and detection of minimal residual disease. A global trend toward multimodal LB approaches, integrating genetic and epigenetic biomarkers, is accelerating clinical transition. Several Food and Drug Administration (FDA)-approved LB tests are already used clinically. PCR-based tests such as Cobas and Idylla™ detect EGFR mutations in cancers such as lung adenocarcinoma. Next-generation sequencing-based platforms such as Guardant360 and FoundationOne Liquid analyze over 70 genes across diverse tumors. In Brazil, despite promising results, the only LB method routinely used is the CellSearch system, limited to metastatic breast, prostate, and colorectal cancers. The application of the LB in public healthcare is constrained by high costs and limited infrastructure. Expanding LB use in Brazil will require investment, cost reduction strategies, and locally validated clinical studies. Globally, further research is essential to fully incorporate LB into clinical oncology and make it accessible to broader patient populations.

Decoding NEC: epigenetic biomarkers for risk stratification and prognosis.

Prostate-specific antigen (PSA) recurrence after radical prostatectomy signifies increased risk of metastasis and death from prostate cancer. Traditional clinical metrics may not accurately capture the underlying biological heterogeneity of the tumour, which might be improved by consideration of epigenetic biomarkers. This study included 293 Australian participants with prostate cancer treated with radical prostatectomy (mean age: 64 years, Gleason score ≥7: 91%). Fourteen tumour DNA methylation-based signatures of aggressiveness and cell division were calculated. The association of epigenetic signatures with clinical variables were assessed using linear regression and risk ratios for PSA recurrence were assessed using modified Poisson regression. Most epigenetic signatures were strongly associated with age, Gleason score, and tumour stage but not with serum PSA levels at diagnosis. Associations were also found with risk of PSA recurrence, with increased risks ranging from 1% to 17% per SD for signatures of clinical variables and 17% to 33% for cell division scores, after adjusting for the main clinicopathological variables. The strongest association was observed for the cell division score RepliTali. Prostate cancer tissue DNA methylation-based signatures of aggressiveness and cell division were associated with elevated risk of PSA recurrence, independently of age and traditional clinicopathological variables.

BackgroundTrisomy 18 (T18, Edwards syndrome) is a lethal chromosomal disorder characterized by multiple congenital anomalies and high perinatal mortality. Although epigenetic alterations have been described in aneuploidy conditions, their causal role in the pathogenesis of T18 remains unclear. This study aimed to characterize genome-wide DNA methylation changes associated with T18 during early development.Material and methodsGenomic DNA was extracted from chorionic villi of five T18 and five euploid fetuses, as well as from normal maternal blood, at 11–13 weeks of gestation. High-resolution methyl-capture sequencing (MC-seq) was performed to profile DNA methylation at approximately 3.2 million CpG sites. Differentially methylated CpG sites (DMCs) and regions (DMRs) were identified. Functional and disease-association enrichment analyses were conducted using multiple bioinformatics tools.ResultsA global trend of DNA hypermethylation was observed in the chorionic villi of T18 fetuses. A total of 6,510 DMCs were identified, including 4,022 hypermethylated and 2,488 hypomethylated CpG sites. Additionally, 301 DMRs were identified, comprising 233 hypermethylated and 68 hypomethylated regions. Notably, chromosome 18, the disease-causing chromosome, contained the highest number of hypermethylated DMRs. Functional enrichment analysis of the 283 genes, including 301 DMRs, revealed significant involvement in biological processes and disease phenotypes relevant to T18, including nervous system development, anatomical structure morphogenesis, and embryonic morphogenesis (adjusted P < 0.001 for all). Among them, 76 DMRs exhibited completely inverse methylation patterns in maternal blood and were identified as potential epigenetic biomarkers for non-invasive prenatal testing of T18.ConclusionsTo our knowledge, this is the first comprehensive MC-seq-based analysis of T18-specific DNA methylation patterns in first-trimester chorionic villi. These findings suggest that DNA methylation changes may represent downstream consequences of chromosomal imbalance in T18 and provide a foundation for future investigations into its pathophysiology and the development of epigenetic biomarkers for early non-invasive detection.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13148-025-02018-4.

Novel FBXW7 hypermethylation in a carboxymethyl lysine- driven retinal co-culture model: An epigenetic biomarker with translational potential for diabetic retinopathy.