Fatty Acid Metabolism as a Potential Therapeutic Target in Thyroid Carcinoma

Abstract

Background: Papillary 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. Methods: Clinical 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, and bioinformatics. Findings: The differentially expressed substances included 146 lipids, 2975 proteins, and 217 metabolites in PTC samples. Multi-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. The key enzymes in the three steps, namely LPL, FATP2, and CPT1A, respectively, were overexpressed. Moreover, their expression was strongly associated with the TNM stage, lymph node metastasis, and PTC prognosis. In addition, the levels of several types of phospholipids and sphingolipids increased significantly in PTC. Interpretation: Our data suggested that enhanced fatty acid metabolism supplied additional energy and substrates for tumour growth, invasion, and metastasis in PTC. This may help elucidate the mechanism underlying PTC pathogenesis and identify the potential therapeutic targets for PTC. Funding Information: Work in the authors' laboratory is supported by grants from National Natural Science Foundation of China (No. 81702647, NO. 81972819), Taishan Scholar Foundation of Shandong Province (No. tspd20181201), Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, Natural Science Foundation of Shandong Province (No. ZR201702190483, No. ZR2020YQ57), Key Technology Research and Development Program of Shandong (No. 2016GSF201161). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This prospective study was approved by the institutional ethical committee of Qilu Hospital of Shandong University, Shandong Province, China. All the specimens were collected in the Qilu Hospital of Shandong University. The participants provided written informed consent for the use of thyroid tissue specimens for research.