The Influence of Glycolytic Enzyme Expression on the Aggressiveness of Papillary Thyroid Carcinoma Using TCGA Data

Abstract

Purpose: Several studies suggest that glycolytic enzyme expression may be linked to increased malignancy in various organs. However, the relationship between glycolytic enzyme expression and aggressiveness in papillary thyroid carcinoma (PTC) is not yet fully understood. This study aimed to determine whether glycolytic enzyme expression correlates with aggressiveness, including lymph node metastasis and extrathyroidal extension, using data from The Cancer Genome Atlas (TCGA). Methods: Lactate dehydrogenase A (LDHA), pyruvate kinase isoform M2 (PKM2), and glucose transporter 1 (GLUT1) mRNA expression were examined in 465 PTC samples using TCGA data. We analyzed the correlation between these glycolytic enzymes and transporter protein and the clinicopathological characteristics of PTC, with a particular focus on lymph node metastasis and recurrence. Results: Overexpression of LDHA, PKM2, and GLUT1 was associated with lymph node metastasis and the aggressive subtype of PTC. In the multivariate analysis, younger age, multifocality, advanced T stage (T3/T4), and increased PKM2 mRNA expression were significant predictors of lymph node metastasis. Among the variables, high PKM2 mRNA expression showed the strongest association with lymph node metastasis (odds ratio 6.907, P=0.001). However, there were no significant differences in disease-free survival rates according to LDHA, PKM2, or GLUT1 expression levels. Conclusion: LDHA, PKM2, and GLUT1 overexpression is linked to lymph node metastasis and aggressive PTC subtypes. Of these, PKM2 mRNA expression may have particular potential as a biomarker for lymph node metastasis in PTC.