Positive prognostic implications of SPHK1 expression in patients with papillary thyroid carcinoma undergoing radioactive iodine therapy.

Sphingosine kinase 1 (SPHK1) is an important enzyme involved in sphingolipid metabolism and has been linked to tumor progression in various cancers. However, its clinical significance in papillary thyroid carcinoma (PTC) remains uncertain. We examined SPHK1 expression using immunohistochemistry on tissue microarrays from 471 patients diagnosed with PTC, with expression levels quantified using the H-score method. SPHK1 positivity, defined as an H-score ≥ 10, was observed in 85 cases (18.0%) and was significantly associated with the BRAF p.V600E mutation (p < 0.001) but not with tumor size, extrathyroidal extension, or lymph node metastasis. In patients younger than 55 years, SPHK1 positivity was associated with improved recurrence-free survival (RFS) (p = 0.046), and this prognostic benefit remained significant in the subgroup receiving radioactive iodine therapy (p = 0.028). Multivariate Cox regression analysis confirmed SPHK1 positivity as an independent predictor of favorable RFS (p = 0.036). Unlike its recognized oncogenic role in other malignancies, SPHK1 may function as a context-dependent biomarker in PTC, particularly among younger patients treated with radioactive iodine, possibly reflecting enhanced immune surveillance or altered tumor–microenvironment interactions. Further investigations are warranted to clarify the immunomodulatory and therapeutic implications of SPHK1 in differentiated thyroid cancer.