Multi-Omics Analysis of Fatty Acid Metabolism in Thyroid Carcinoma

被引:26
|
作者
Lu, Jinghui [1 ]
Zhang, Yankun [2 ,3 ]
Sun, Min [1 ,4 ]
Ding, Changyuan [5 ]
Zhang, Lei [6 ]
Kong, Youzi [7 ,8 ]
Cai, Meng [9 ]
Miccoli, Paolo [10 ]
Ma, Chunhong [2 ,3 ]
Yue, Xuetian [7 ,8 ]
机构
[1] Shandong Univ, Dept Hernia & Abdominal Wall Surg, Gen Surg, Qilu Hosp,Cheeloo Coll Med, Jinan, Peoples R China
[2] Shandong Univ, Key Lab Expt Teratol, Minist Educ, Sch Basic Med Sci,Cheeloo Coll Med, Jinan, Peoples R China
[3] Shandong Univ, Dept Immunol, Sch Basic Med Sci, Cheeloo Coll Med, Jinan, Peoples R China
[4] Shandong Univ, Lab Basic Med Sci, Qilu Hosp, Cheeloo Coll Med, Jinan, Peoples R China
[5] Shandong Univ, Dept Thyroid Surg, Gen Surg, Qilu Hosp,Cheeloo Coll Med, Jinan, Peoples R China
[6] Shandong Univ, Dept Obstet, Second Hosp, Cheeloo Coll Med, Jinan, Peoples R China
[7] Shandong Univ, Key Lab Expt Teratol, Minist Educ, Sch Basic Med Sci,Cheeloo Coll Med, Jinan, Peoples R China
[8] Shandong Univ, Dept Cell Biol, Sch Basic Med Sci, Cheeloo Coll Med, Jinan, Peoples R China
[9] Shandong First Med Univ, Dept Ultrasound, Shandong Prov Hosp, Jinan, Peoples R China
[10] Univ Pisa, Dept Surg, Pisa, Italy
来源
FRONTIERS IN ONCOLOGY | 2021年 / 11卷
基金
中国国家自然科学基金;
关键词
fatty acid metabolism; multi-omics analysis; thyroid carcinoma; therapeutic target; FATP2; CPT1A; LPL; ACYL-COA SYNTHETASE; LIPOPROTEIN-LIPASE; LIPID-METABOLISM; TRANSPORT; CANCER; SURVIVAL;
D O I
10.3389/fonc.2021.737127
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:12
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