DNA Methylation-Based Method to Differentiate Malignant from Benign Thyroid Lesions

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Fine-needle aspiration biopsy (FNAB) for thyroid nodules has diagnostic limitations.
• Molecular markers can enhance FNAB accuracy and prevent unnecessary surgeries.
• Identifying reliable DNA methylation biomarkers is crucial for thyroid lesion diagnosis.

Purpose of the Study:

• To identify DNA methylation biomarkers for thyroid lesions.
• To develop a diagnostic tool for differentiating benign from malignant thyroid nodules.
• To assess the clinical applicability of the developed diagnostic tool.

Main Methods:

• Genome-wide DNA methylation profiling (Illumina 450K) was performed on papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), non-neoplastic thyroid tissue (NT), and benign thyroid lesions (BTL).
• Results were validated using publicly available datasets (GEO, TCGA).
• Six differentially methylated CpGs were selected and evaluated using bisulfite-pyrosequencing in surgical specimens and FNAB samples.

Main Results:

• DNA methylation analysis identified numerous differentially methylated CpGs in PTC and FTC compared to benign and non-neoplastic tissues.
• A diagnostic classifier based on six CpGs demonstrated high sensitivity (94.3%) and specificity (82.4%) in differentiating benign from malignant thyroid lesions.
• The tool showed consistent performance across external datasets and in validation using bisulfite-pyrosequencing, including in FNAB samples with indeterminate cytology.

Conclusions:

• A novel diagnostic tool utilizing DNA methylation biomarkers for thyroid nodules has been developed.
• This tool shows significant potential for preoperative screening, improving diagnostic accuracy.
• The proposed protocol may help avoid unnecessary thyroidectomies by providing more precise diagnoses.