SLC12A4 promoter methylation in plasma cell-free DNA as a candidate biomarker for thyroid cancer
Year: 2026
Type: article
Abstract: Background: Plasma cell-free DNA (cfDNA) methylation has emerged as a promising non-invasive approach for cancer detection; however, methylation biomarkers for thyroid carcinoma (THCA) remain insufficiently defined. This study aimed to identify THCA-associated DNA methylation alterations and evaluate their potential diagnostic value in plasma cfDNA. Methods: promoter region (chr16:67997880-67998180) was evaluated by methyl-CpG binding domain sequencing (MBD-seq) in tissue and plasma samples. Exploratory plasma diagnostic analyses were performed in seven patients with papillary thyroid carcinoma (PTC), together with control and non-THCA comparator samples. Results: promoter methylation enrichment in THCA tissues, with a similar directional pattern observed in four of five matched tumor-adjacent pairs, and the methylation signal was detectable in plasma cfDNA. In the exploratory comparison of seven PTC plasma samples with 1,301 normal controls, the area under the curve (AUC) was 0.938 [95% confidence interval (CI): 0.879-0.997]. At the exploratory cut-off of 12.2093 fragments per kilobase of exon model per million mapped fragments (FPKM), sensitivity was 0.857 (95% CI: 0.421-0.996) and specificity was 0.925 (95% CI: 0.909-0.938). These estimates should be interpreted as exploratory and require confirmation in independent cohorts. Conclusions: promoter methylation as a candidate plasma biomarker for further evaluation, particularly in PTC. Validation in larger independent cohorts, including clinically relevant benign thyroid disease controls, is warranted.
Source: Translational Cancer Research
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223972780