ArticleBMC cancer2022
Global DNA hypomethylation of colorectal tumours detected in tissue and liquid biopsies may be related to decreased methyl-donor content.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Epigenetic modulation of autophagy pathway by small molecules in colorectal cancer: a systematic review.Journal of cancer research and clinical oncology · 2024Pooled it
- Folate deficiency modifies the risk of CIN3+ associated with DNA methylation levels: a nested case-control study from the ASCUS-COL trial.European journal of nutrition · 2024Trial
- Article
- FFAR4 negatively regulates colorectal cancer growth via blocking oxidative phosphorylation.Journal of translational medicine · 2026Article
- DMN-seq enriches DNA hypomethylated regions for biomarker discovery using 5-methylcytosine glycosylase.Genome biology · 2026Article
- SLC46A1 deficiency-mediated folate restriction suppresses colorectal cancer progression through epigenetic-transcriptional reprogramming.Cell death & disease · 2026Article
- Understanding Cancer Health Disparities.Cancers · 2026Review
- Genome-wide extraction of differentially methylated DNA regions using adapter-anchored proximity primers.Nucleic acids research · 2026Article
- Serum DIP2C protein concentration in human colorectal cancer among Yemeni patients.Frontiers in oncology · 2026Article
- Global Hypomethylation in Cell-Free DNA Enables Noninvasive Colorectal Cancer Screening: Results from a Retrospective Validation Study.Computational and structural biotechnology journal · 2026Article
- Atorvastatin suppresses high-risk colorectal adenomas via reprogramming of lipid metabolism and Inhibition of stemness.Scientific reports · 2025Article
- Multi-omics analyses integration reveals a novel TRF2-miR-181a-5p-S100A10 regulatory axis in colon cancer.Cellular & molecular biology letters · 2025Article
- Plasmonic Molecular Entrapment for Label-Free Methylated DNA Detection and Machine-Learning Assisted Quantification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Long interspersed nuclear element 1 methylation in non-small cell lung cancer: implications for diagnosis, prognosis, and therapeutic targeting.Cell communication and signaling : CCS · 2025Review
- Review
- Integrated transcriptomic analysis reveals a CEBPB-DUSP1 axis driving tumor progression in colorectal cancer.PloS one · 2025Article
- Article
- Review
- Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer.Journal of gastrointestinal cancer · 2024Article
- Prolonged culturing of colonic epithelial organoids derived from healthy individuals and ulcerative colitis patients results in the decrease of LINE-1 methylation level.Scientific reports · 2024Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundHypomethylation of long interspersed nuclear element 1 (LINE-1) is characteristic of various cancer types, including colorectal cancer (CRC). Malfunction of several factors or alteration of methyl-donor molecules' (folic acid and S-adenosylmethionine) availability can contribute to DNA methylation changes. Detection of epigenetic alterations in liquid biopsies can assist in the early recognition of CRC. Following the investigations of a Hungarian colon tissue sample set, our goal was to examine the LINE-1 methylation of blood samples along the colorectal adenoma-carcinoma sequence and in inflammatory bowel disease. Moreover, we aimed to explore the possible underlying mechanisms of global DNA hypomethylation formation on a multi-level aspect.
methodsLINE-1 methylation of colon tissue (n = 183) and plasma (n = 48) samples of healthy controls and patients with colorectal tumours were examined with bisulfite pyrosequencing. To investigate mRNA expression, microarray analysis results were reanalysed in silico (n = 60). Immunohistochemistry staining was used to validate DNA methyltransferases (DNMTs) and folate receptor beta (FOLR2) expression along with the determination of methyl-donor molecules' in situ level (n = 40).
resultsSignificantly decreased LINE-1 methylation level was observed in line with cancer progression both in tissue (adenoma: 72.7 ± 4.8%, and CRC: 69.7 ± 7.6% vs. normal: 77.5 ± 1.7%, p ≤ 0.01) and liquid biopsies (adenoma: 80.0 ± 1.7%, and CRC: 79.8 ± 1.3% vs. normal: 82.0 ± 2.0%, p ≤ 0.01). However, no significant changes were recognized in inflammatory bowel disease cases. According to in silico analysis of microarray data, altered mRNA levels of several DNA methylation-related enzymes were detected in tumours vs. healthy biopsies, namely one-carbon metabolism-related genes-which met our analysing criteria-showed upregulation, while FOLR2 was downregulated. Using immunohistochemistry, DNMTs, and FOLR2 expression were confirmed. Moreover, significantly diminished folic acid and S-adenosylmethionine levels were observed in parallel with decreasing 5-methylcytosine staining in tumours compared to normal adjacent to tumour tissues (p ≤ 0.05).
conclusionOur results suggest that LINE-1 hypomethylation may have a distinguishing value in precancerous stages compared to healthy samples in liquid biopsies. Furthermore, the reduction of global DNA methylation level could be linked to reduced methyl-donor availability with the contribution of decreased FOLR2 expression.
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