Epigenomic profiling of papillary thyroid carcinoma reveals distinct subtypes with clinical implications.

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer with generally favorable outcomes. However, surgeons often face challenges regarding optimal surgical timing, extent of surgery, and identifying patients at risk for metastasis or progression to more aggressive subtypes. The ongoing debate over immediate surgery versus active surveillance emphasizes the need for reliable, minimally invasive diagnostic tools to inform surgical decision-making. This study aims to develop an epigenetic biomarker-based prediction system using fine-needle aspiration biopsy (FNAB) samples to assess PTC aggressiveness preoperatively. We conducted a comprehensive analysis of methylome data to identify approximately 7200 CpG islands with altered methylation levels in thyroid cancer tissues. These candidate regions were further examined in our cohort of 55 PTC patients to develop methylation-specific primers suitable for FNAB samples. Methylation patterns allowed us to stratify patients into two distinct prognostic groups, one of which exhibited a poorer survival rate. Our methylation-specific primers effectively classified FNAB samples into these groups, demonstrating their potential as a preoperative tool for assessing tumor aggressiveness. This stratification aids in informing surgical planning and personalizing treatment strategies. DNA methylation profiling of PTC identifies key epigenetic biomarkers associated with tumor aggressiveness. Utilizing these biomarkers in FNAB samples provides a minimally invasive method for preoperative risk assessment, assisting surgeons in tailoring surgical interventions and potentially improving patient outcomes.