Polyamine and Methionine Metabolism Gene Expression Analysis in Thyroid Tumors

Introduction

• Polyamines are small organic cations that are essential for normal cell growth and development.¹
• Polyamine levels are elevated in thyroid cancers and highest in poor prognostic subtypes including poorly differentiated and anaplastic thyroid cancers. Methionine, a methyl donor and nutrient important for nucleic acid synthesis, is an essential precursor for polyamine synthesis.
• We hypothesized that polyamine-methionine cycle gene expression may be directly correlated with thyroid tumor cytologic, molecular, and clinical risk (Figure 1).²

Methods

• The Afirma Genomic Sequencing Classifier (GSC) exome-enriched RNAseq database was analyzed for polyamine and methionine metabolism gene expression from cytologically indeterminate ((B)ethesda III/IV – ITN) molecularly benign (GSC-B) (n=30,259), molecularly suspicious (GSC-S) (n=15,815), and malignant (BV/VI, n=1,621) fine needle biopsy specimens (Table 1).
• Patient samples with Afirma testing from an integrated interventional thyroid practice (n=464) were analyzed to assess the correlation between polyamine and methionine gene expression and histopathologic features including vascular invasion and lymph node metastasis (Table 1).

Conclusion

• Higher expression of methionine salvage pathway genes is associated with greater cytologic risk and clinically aggressive behavior whereas polyamine catabolism gene expression confers less risk.
• Future work seeks to leverage these data to further risk stratify those patients with ITN and molecularly suspicious tumors who may be more likely to present with clinically aggressive thyroid cancer warranting closer surveillance.