The effect of glycolytic enzyme expression and thyroiditis on the aggressiveness of papillary thyroid carcinoma: a retrospective cohort study

Abstract

Purpose: Glycolytic enzymes have been extensively studied in various cancer types, revealing their aggressive characteristics and roles in tumor progression. This study aimed to determine whether the expression of glycolytic enzymes is associated with aggressiveness in the presence or absence of chronic lymphocytic thyroiditis (CLT). Methods: The expression of hexokinase 2, lactate dehydrogenase A (LDHA), pyruvate kinase isoform M2 (PKM2), glucose transporter 1 (GLUT1), and monocarboxylate transporter 4 (MCT4) was examined in 233 papillary thyroid carcinoma (PTC) specimens by immunohistochemistry. We evaluated whether the expression of these glycolytic enzymes correlates with lymph node metastasis, extrathyroidal extension (ETE), and recurrence rate, both with and without CLT. In addition, we analyzed the correlation between glycolytic enzyme messenger RNA expression and risk factors in PTC using The Cancer Genome Atlas. Results: All glycolytic enzymes and transporter proteins were overexpressed in PTC compared with normal tissue. PKM2 expression was most highly correlated with the other glycolytic enzymes. High PKM2 expression was significantly linked to increased recurrence risk in patients without CLT (hazard ratio, 1.76; 95% confidence interval, 1.01-3.06; P = 0.046), but this association was not observed in those with CLT. Conclusion: Overexpression of LDHA, PKM2, GLUT1, and MCT4 is associated with PTC. CLT is significantly associated with an increased incidence of gross ETE and, paradoxically, with a reduced recurrence rate in PTC. LDHA expression was lower in the presence of CLT, whereas PKM2 remained consistently linked to a higher recurrence rate in its absence. Among the evaluated glycolytic enzymes, PKM2 may serve as a biomarker for recurrence in PTC. [Ann Surg Treat Res 2025;109(3):169-184]