Abstract

ObjectivePapillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancer and affects a large number of individuals. The pathogenesis of PTC has not been completely elucidated thus far. Metabolic reprogramming is a common feature in tumours. Our previous research revealed the reprogramming of lipid metabolism in PTC. Further studies on lipid metabolism reprogramming may help elucidate the pathogenesis of PTC.MethodsClinical samples of PTC and para-tumour tissue were analysed using lipidomic, proteomic, and metabolomic approaches. A multi-omics integrative strategy was adopted to identify the important pathways in PTC. The findings were further confirmed using western blotting, tissue microarray, bioinformatics, and cell migration assays.ResultsMulti-omics data and the results of integrated analysis revealed that the three steps of fatty acid metabolism (hydrolysis, transportation, and oxidation) were significantly enhanced in PTC. Especially, the expression levels of LPL, FATP2, and CPT1A, three key enzymes in the respective steps, were elevated in PTC. Moreover, LPL, FATP2 and CPT1A expression was associated with the TNM stage, lymph node metastasis of PTC. Moreover, high levels of FATP2 and CPT1A contributed to poor prognosis of PTC. In addition, ectopic overexpression of LPL, FATP2 and CPT1A can each promote the migration of thyroid cancer cells.ConclusionsOur data suggested that enhanced fatty acid metabolism supplied additional energy and substrates for PTC progression. This may help elucidating the underlying mechanism of PTC pathogenesis and identifying the potential therapeutic targets for PTC.

Highlights

  • The incidence of thyroid carcinoma has increased rapidly in recent years

  • We evaluated the characteristics of fatty acid (FA) metabolism in Papillary thyroid carcinoma (PTC), which may help clarifying the pathogenesis of PTC

  • The evidence indicated that PTC was considerably influenced by lipid metabolism

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Summary

Introduction

The incidence of thyroid carcinoma has increased rapidly in recent years. Papillary thyroid carcinoma (PTC) accounts for 80% of all cases of thyroid malignancies [1, 2]. Patients with PTC exhibit relatively good prognosis and low mortality after standard treatment, the recurrence rate is considerably high at 20%–30%, or even higher, in some subtypes of PTC [3]. Some patients may die owing to their inability to undergo surgery or iodine-131 treatment at advanced tumour stages. There are no effective preventive methods or medical resources that can be used. The pathogenesis of PTC remains unclear and can be confirmed only via thorough investigation

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