Metabolomics In Female Papillary Thyroid And Benign Thyroid Adenoma

Objective.The incidence of thyroid nodules has dramatically increased.However,the metabolic profiling about malignant or benign thyroid nodules have not been characterized,whether in the tissues or in the plasma.The aims of this study were to identify the metabolic profiles of the female papillary thyroid carcinoma(PTC)and the relationship between the metabolism and tumor size and the cervical lymph node metastasis.In addition,we evaluated the variation in plasma free amino acids(PFAA)in patient with PTC、benign thyroid adenoma(BTA)and health controls.Methods.1.Tumors and adjacent nontumor specimens collected from 43 female patients with PTC were profiled using GC-TOFMS(gas chromatography–time-of-flight mass spectrometry)and UPLC-QTOFMS(ultra performance liquid chromatography-time of flight-mass spectrometry).Multi-/uni-variate statistical methods were used for group differentiation and potential biomarkers selection.Moreover,Forty-three samples were divided into Group T1(tumor size ≤ 2.0 cm)and Group T2(tumor size > 2.0 cm)according to tumor size and into Group N–(negative cervical lymph nodes)and Group N+(positive cervical lymph nodes)according to the cervical lymph node status.Multivariate statistical methods were used to discriminate between the T and between the N groups.2.The free amino acids content of 30 plasma samples from age-/BMI-matched female PTC、 BTA and health control were determined by amino acid analyzer.The results were analyzed by multi-/uni-variate statistical method.Result.1.A total of 46 metabolites showing significant differences in PTC tumor tissues compared with their adjacent normal tissues in females were identified.We also identified four metabolites(leucine,uracil,cysteine,putrescine)closely related to PTC tumor size and two metabolites(citric acid,7-methyl xanthine)closely correlated with lymph node metastases.2.Common changes to both female PTC and BTA patients plasma were present at lower levels acid amino,including: Met,Leu,Phe,Gly,Arg and EOHNH2,while only Cys was at an elevated levels,compared to healthy plasmas.However,the patients with BTA and PTC couldn’t be discriminated by PFAAs profiling,indicating that BTA simultaneously displayed familiar PFAAs features of PTC.3 PFAA were at lower levels in PTC than in health controls only,including Val,Ala and Tyr.6 PFAA,including Thr,Asp,Ser,Glu,αAAA and AspNH2,were decreased in BTA compared to health controls.Conclusion.1.The metabolic profiles in female PTC tissue were significantly different from those in adjacent normal tissues,as determined by GC–TOFMS and UPLC–QTOFMS.We found enhanced levels of amino acid metabolism,glycolysis,purine and pyrimidine metabolism,tryptophan metabolism,one-carbon unit metabolism,and taurine and hypotaurine metabolism in PTC tumor specimens.In addition,there were strong correlations between metabolic profiles and tumor size in PTC as well as lymph node metastasis.Increased levels of leucine,uracil,cysteine,and putrescine were closely related to a larger tumor size in female PTC patients.Decreased levels of citric acid and increased levels of 7-methylxanthine were correlated with lymph node metastasis in PTC of female patients.2.PFAAs profiles have a great potential for screening and diagnosis and understanding thyroid cancer pathogenesis.Common PFAAs profiles associating with BTA and PTC were decreased in amino acid content,indicating a disturbed protein metabolism in the plasma in both female PTC and BTA patients.BTA was found to display a similar PFAAs profiles with PTC,suggesting that BTA may be an individual stage of PTC development.