ArticleWorld journal of surgical oncology2025
ctDNA methylation profiling reveals NBL1 as a promising biomarker for early ovarian cancer screening.
Article in World journal of surgical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- DNA methylation biomarkers for early detection of ovarian cancer.Molecular biology reports · 2026Review
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5 authors.
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Abstract
backgroundEarly detection of epithelial ovarian cancer (EOC) is crucial for improving patient survival. Current screening methods have limitations, highlighting the need for novel biomarkers. Circulating tumor DNA (ctDNA) methylation analysis offers a promising approach.
methodsThis study included 10 patients with EOC and 10 patients with benign pelvic masses. We collected plasma samples from these patients and isolated ctDNA. We then conducted whole-genome methylation sequencing using the TAPS (TET-assisted pyridine borane sequencing) method, which allows for single-base resolution detection of 5-methylcytosine and 5-hydroxymethylcytosine. Bioinformatics analysis was performed to identify differentially methylated genes and regions. We further validated candidate biomarkers using bisulfite sequencing, qRT-PCR, and IHC. TCGA methylation data were analyzed for external validation.
resultsWe identified 35 differentially methylated genes, with NBL1 and CASZ1 as potential candidates. NBL1 gene hypermethylation in EOC patients was significantly associated with reduced mRNA expression, suggesting its role as a tumor suppressor gene. CASZ1 methylation patterns were inconsistent between blood and tissue, indicating limited utility as a diagnostic biomarker. We also observed widespread hypo-methylation across the genome and hyper-methylation in specific regions of differential methylation. GO and KEGG pathway enrichment analyses revealed that the differentially methylated genes were involved in various biological processes and pathways relevant to cancer pathogenesis. There is a significant negative correlation between the methylation level and the mRNA level of the NBL1 gene, suggesting that hypermethylation of the NBL1 gene may be associated with a reduction in its expression. Furthermore, immunohistochemical analysis indicates a downregulation of NBL1 expression in ovarian cancer tissues, which contrasts with the strong positive expression observed in benign tissues.
conclusionOur study demonstrates the potential of ctDNA methylation analysis for early EOC detection. we propose that NBL1 gene hold potential as screening biomarkers for ovarian cancer.
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