MeIS: DNA Methylation-Based Immune Response Signatures for Thyroid Nodule Diagnostics

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Distinguishing benign thyroid nodules (BTNs) from papillary thyroid cancers (PTCs) remains a clinical challenge.
• Current diagnostic methods often lack definitive accuracy for indeterminate thyroid nodules.

Purpose of the Study:

• To identify DNA methylation markers of immune response-related genes for improved BTN and PTC differentiation.
• To develop and validate a diagnostic classifier based on these methylation markers.

Main Methods:

• Analysis of reduced representative bisulfite sequencing data to identify distinct methylation patterns.
• Development of the Methylation-based Immune Response Signature (MeIS) classifier using 15 DNA methylation markers.
• Validation of MeIS performance in independent retrospective and preoperative cohorts.

Main Results:

• The MeIS classifier achieved high diagnostic performance, with AUCs ranging from 0.89 to 0.98 across cohorts.
• MeIS demonstrated significant sensitivity and specificity for indeterminate thyroid nodules (e.g., 91% sensitivity, 82% specificity in one cohort).
• Combined MeIS and BRAF V600E detection further enhanced diagnostic accuracy for indeterminate nodules.

Conclusions:

• The identified 15 DNA methylation markers offer a promising tool for improving the diagnosis of indeterminate thyroid nodules.
• The MeIS classifier provides a novel, methylation-based approach for thyroid nodule differentiation.
• Integration with genetic markers like BRAF V600E can further refine diagnostic capabilities.