A machine learning-based method for feature reduction of methylation data for the classification of cancer tissue origin DOI Creative Commons
Marco A. De Velasco, Kazuko Sakai, Seiichiro Mitani

et al.

International Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Abstract Background Genome DNA methylation profiling is a promising yet costly method for cancer classification, involving substantial data. We developed an ensemble learning model to identify types using profiles from limited number of CpG sites. Methods Analyzing data 890 samples across 10 the TCGA database, we utilized ANOVA and Gain Ratio select most significant sites, then employed Gradient Boosting reduce these just 100 Results This approach maintained high accuracy multiple machine models, with classification rates between 87.7% 93.5% methods including Extreme Boosting, CatBoost, Random Forest. effectively minimizes features needed without losing performance, helping classify primary organs uncover subgroups within specific cancers like breast lung. Conclusions Using gradient boosting feature selector shows potential streamlining methylation-based classification.

Language: Английский

Aberrant DNA methylation as a key modulator of cell death pathways: insights into cancer progression and other diseases DOI

Ambreen Zahoor,

Rafia Khazer,

Insha Mehraj

et al.

Functional & Integrative Genomics, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 1, 2025

Language: Английский

Citations

2

Cellular Epigenetic Targets and Epidrugs in Breast Cancer Therapy: Mechanisms, Challenges, and Future Perspectives DOI Creative Commons

Ibrahim S. Alalhareth,

Saleh M. Alyami,

Abdulrhman Alshareef

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 207 - 207

Published: Feb. 3, 2025

Breast cancer is the most common malignancy affecting women, manifesting as a heterogeneous disease with diverse molecular characteristics and clinical presentations. Recent studies have elucidated role of epigenetic modifications in pathogenesis breast cancer, including drug resistance efflux characteristics, offering potential new diagnostic prognostic markers, treatment efficacy predictors, therapeutic agents. Key include DNA cytosine methylation covalent modification histone proteins. Unlike genetic mutations, reprogramming landscape epigenome promising targeted therapy for reversal resistance. Epidrugs, which target modifications, can provide novel options by reversing acquired to treatment. Currently, approach involves combination therapies consisting epidrugs immune checkpoint inhibitors. This review examines aberrant regulation initiation progression, focusing on related estrogen signaling, resistance, epithelial–mesenchymal transition (EMT). It existing drugs treating agents that modify DNA, inhibitors acetyltransferases, deacetylases, methyltransferases, demethyltransferases. also delves into ongoing combining other addresses upcoming obstacles this field.

Language: Английский

Citations

1

CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches DOI Creative Commons
Louis Boafo Kwantwi,

James Danquah Boafo,

Bevelyn Emefa Egleh

et al.

Clinical & Translational Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Abstract Increasing knowledge of the immunosuppressive tumor microenvironment in cancer-related processes has led to developing novel immune-based therapies that have changed cancer treatment paradigm. In microenvironment, plethora soluble factors secreted by cells interacts with immune and non-immune components deliver signals necessary for progression. Accordingly, targeting tumor-derived inducing this become an appealing therapeutic potential advancing treatment. CCL20, a chemokine best known induce leucocyte migration response pathological inflammatory conditions, been implicated proliferation, angiogenesis, metastasis, immunosuppression, resistance. Notably, CCL20 its receptor CCR6 are important interactions. This review discusses interaction between CCL20–CCR6 axis how these interactions promote Also, outline studies utilizing combination other standard treatments shed.

Language: Английский

Citations

1

CRISPR/Cas-mediated macromolecular DNA methylation editing: Precision targeting of DNA methyltransferases in cancer therapy DOI

Feng Chena,

Lu Chenb

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142401 - 142401

Published: March 1, 2025

Language: Английский

Citations

1

Targeted demethylation of the EphA7 promoter inhibits tumorigenesis via the SP1/DNMT1 and PI3K/AKT axes and improves the response to multiple therapies in cervical cancer DOI Creative Commons

Wenfan Zhang,

Jing Zhao,

Xueting Fan

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 21, 2025

Abstract Aberrant methylation of the EphA7 promoter has been observed in cervical cancer (CC); however, its precise function and role CC remain largely unknown. In this study, we investigated molecular mechanisms carcinogenesis. First, our results indicated that reactivation expression via a CRISPR demethylation tool (dCas9-Tet1) had antitumor effects. It restrained tumor proliferation invasion while promoting apoptosis PI3K/AKT signaling pathway both CaSki SiHa cells. The upstream interacting factors were subsequently captured by CRISPR-mediated pull-down situ, result revealed SP1 MAZ interacted with EphA7. However, perturbation was associated SP1/DNMT1 but not MAZ. Furthermore, 17-β-estradiol (E2) can upregulate through axis. A rescue experiment interference could restore effect E2 on increasing upregulating estrogen receptor expression. addition, reduced half-maximal inhibitory concentration (IC 50 ) cisplatin paclitaxel. Pooled analysis hypermethylation positively correlated purity negatively immune cell infiltration, cytotoxic T lymphocyte (CTL) checkpoint (IC) activity, significantly mutational burden (TMB), microsatellite instability (MSI) presence single nucleotide variant (SNV) neoantigens, suggesting better prognosis for patients hypomethylation high Collectively, these findings indicate targeted restoration endogenous dCas9-Tet1 are promising therapeutic approaches favorable patients.

Language: Английский

Citations

1

Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment DOI Creative Commons
Kang Liu, Yue Li, Minmin Shen

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 71 - 71

Published: Jan. 6, 2025

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes suppressor genes transformed cells, significantly contributes to development at both primary distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues downstream signals, altering phenotype stromal cells immune cells. This remolds area surrounding ultimately fostering an immunosuppressive microenvironment. Therefore, correcting TME by targeting modifications holds substantial promise for cancer treatment. review synthesizes recent research that elucidates impact specific regulations-ranging from DNA methylation histone chromatin remodeling-on within TME. Notably, we highlight their functional roles either promoting or restricting We also discuss potential applications agents treatment, envisaging ability normalize ecosystem. aims assist researchers understanding dynamic interplay between epigenetics TME, paving way better therapy.

Language: Английский

Citations

0

Exploring Methylation Signatures for High De Novo Recurrence Risk in Hepatocellular carcinoma DOI Creative Commons
Da-Won Kim,

Jin Hyun Park,

Suk Kyun Hong

et al.

Clinical and Molecular Hepatology, Journal Year: 2025, Volume and Issue: 31(2), P. 563 - 576

Published: Jan. 14, 2025

Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery prediction methods are limited, emphasizing the need for reliable biomarkers to assess risk. We aimed develop methylation-based markers classifying HCC patients and predicting their risk of post-surgery. In this retrospective cohort study, we analyzed data from who underwent surgical resection in Korea, excluding those with within one year Using Infinium Methylation EPIC array on 140 samples discovery cohort, classified into low- high-risk groups based methylation profiles. Distinctive were identified through random forest analysis. These validated cancer genome atlas (n=217), Validation 1 (n=63) experimental using a methylation-sensitive high-resolution melting (MS-HRM) assay 2 (n=63). The low-risk group (methylation 1; MG1) showed average 0.73 (95% confidence interval [CI] 0.69-0.77) 23.5% rate, while (MG2) had an 0.17 CI 0.14-0.20) 44.1% rate (P<0.03). confirmed applicability across diverse populations, showing accuracy probability (area under curve 96.8%). MS-HRM its effectiveness 95.5% sensitivity, 89.7% specificity, 92.2% accuracy. effectively by risk, enhancing potentially offering personalized management strategies.

Language: Английский

Citations

0

The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment DOI Creative Commons
Dae Joong Kim

Current Oncology, Journal Year: 2025, Volume and Issue: 32(2), P. 88 - 88

Published: Feb. 5, 2025

Members of the DNA methyltransferase (DNMT) family have been recognized as major epigenetic regulators altered gene expression during tumor development. They establish and maintain methylation CpG island promoter non-CpG region genome. The abnormal status suppressor genes (TSGs) has associated with tumorigenesis, leading to genomic instability, improper silence, immune evasion. DNMT1 helps preserve patterns replication, whereas DNMT3 is responsible for de novo methylation, creating new patterns. Altered significantly supports growth by changing FDA-approved DNMT inhibitors reverse hypermethylation-induced repression improve therapeutic outcomes cancer. Recent studies indicate that combining chemotherapies immunotherapies can synergistic effects, especially in aggressive metastatic tumors. Improving treatment schedules, increasing isoform specificity, reducing toxicity, utilizing genome-wide analyses CRISPR-based editing create personalized therapies tailored individual patient needs are promising strategies enhancing outcomes. This review discusses interaction between DNMT1, its binding partners, connection tumors, how these processes contribute development, inhibitors’ advancements pharmacological properties.

Language: Английский

Citations

0

Emerging Mechanisms and Biomarkers Associated with T-Cells and B-Cells in Autoimmune Disorders DOI
Azhagu Madhavan Sivalingam

Clinical Reviews in Allergy & Immunology, Journal Year: 2025, Volume and Issue: 68(1)

Published: Feb. 11, 2025

Language: Английский

Citations

0

Carbon nanodots derived from herbal extract ginsenoside Rg1 demonstrate highly effective inhibition against cervical carcinoma DOI
Jiahui Bao,

Xuechun Zhou,

Xiaoyu He

et al.

Carbon letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

0