Background Patients with papillary thyroid carcinoma (PTC) generally have a favorable prognosis, but some may develop lymph node metastasis. However, effective methods for predicting lymph node metastasis in PTC are still lacking.

Objective To explore the correlation between high-risk molecular subtypes of PTC and lymph node metastasis (LNM) by molecular risk group (MRG).

Methods Genetic testing was performed using next-generation sequencing technology (NGS) on postoperative specimens of PTC patients who underwent surgery in the Department of Thyroid (Hernia) Surgery, the First Medical Center of PLA General Hospital from November 2021 to March 2024. Molecular risk stratification was performed for 39 genetic variants, while clinicopathological data of the patients were collected. Logistic regression analysis was conducted to identify factors associated with lymph node metastasis, and the predictive performance of the molecular risk gene (MRG) was evaluated.

Results A total of 74 PTC patients were enrolled, including 23 males (31.1%) and 51 females (68.9%). The age ranged from 17 to 69 years, with a median age of (40.16±12.59) years. A total of 39 gene mutations were detected in 74 PTC patients, including 37 SNV/Indel and 2 fusion genes, with a mutation rate of 100%. MRG high-risk classification was found in 38 cases (51.35%) and low-risk classification in 36 cases (48.65%). The relationship between MRG classification and clinicopathological features of papillary thyroid carcinoma showed that the presence of capsular invasion was significantly related to MRG high-risk classification (P=0.035). Multivariate Logistic regression analysis showed that MRG high-risk classification was an independent risk factor for LNM/CLNM/LLNM in PTC patients (OR=3.080/2.545/1.443, P < 0.05). Paired four-grid table analysis showed that MRG high-risk classification had a certain evaluation efficacy for lymph node metastasis, central lymph node metastasis and lateral cervical lymph node metastasis, and the AUC was 0.729, 0.671 and 0.601, respectively. Statistical inference showed that MRG high-risk classification was significantly associated with lymph node metastasis/central lymph node metastasis (P < 0.05), but the dominance (difference test) was also significant (P < 0.05), suggesting that it was different from the gold standard.

Conclusion MRG high-risk classification is associated with central lymph node metastasis in PTC by molecular risk stratification method. MRG high-risk classification may be a potential indicator for predicting central lymph node metastasis in PTC, which is a new method for preoperative evaluation of central lymph node metastasis in PTC patients.