PCSK9 and Thyroid Tumor Dynamics: Exploring the Metabolic–Oncogenic Interface in PTC Patients ^†

Introduction: PCSK9 encodes a protein that regulates cholesterol homeostasis by promoting degradation of the low-density lipoprotein receptor (LDLR), thereby increasing plasma LDL-cholesterol levels and influencing cardiovascular risk. Emerging evidence suggests that LDLR also contributes to tumor progression, particularly in papillary thyroid carcinoma (PTC), where its overexpression enhances LDL uptake and activates the RAS/RAF/MEK/ERK pathway—especially in tumors harboring the aggressive BRAF V600E mutation. This study investigated the association between the PCSK9 E670G variant and clinical parameters in PTC, exploring its potential as a biomarker at the intersection of lipid metabolism and oncogenesis. Methodology: This pilot study included 11 PTC patients from the Federal District (UniCEUB Ethics Committee-CAAE No. 57382416.6.0000.0023). The PCSK9 E670G variant was genotyped from patients’ extracted peripheral blood DNA using the PCR-RFL method. Statistical analysis employed Pearson’s chi-square and Mann–Whitney U tests (p < 0.05). Results: Nine patients with the AA genotype (81.8%) were identified in the group, and 18.2% had the AG genotype. Among PTC patients, the AA genotype was more frequent in those receiving intermediate radioiodine doses and in early tumor stages (T1+T2). AA carriers were evenly distributed between N0 and N1 lymph node status, while AG carriers were predominantly N1. Women were more prevalent in the RR group. Conclusions: Although no statistically significant associations were identified, genotype-related patterns suggest potential clinical relevance of PCSK9 in thyroid cancer, warranting further investigation in larger cohorts.