| Background and objectiveIn recent years,the incidence of thyroid cancer(TC)has increased significantly worldwide,and the disease burden has become increasing.Although ultrasound-guided fine-needle aspiration cytology is the "gold standard",approximately 20%of the pathological examination results were inconclusive,and the fine-needle aspiration is prone to missed diagnoses caused by limited access range.In this study,serum specific markers for papillary thyroid cancer(PTC)and the risk association and the possible mechanisms between metabolites levels and PTC were explored from the perspective of metabolomics with the aim of providing a scientific basis for application in the early detection and diagnosis and precise prevention of PTC.Research methods1.Study subjects:170 patients with first diagnosed PTC and 60 patients with papillary thyroid microcarcinoma(PTMC)were recruited from 3A grade hospitals in Shenzhen,of which total 230 case-control pairs were matched by gender and age(±2 years)in this study.2.Methods:Fasting serum of study subjects surveyed by questionnaire was collected,then subjected to clinical examination and laboratory investigations.The differential metabolites were identified by untargeted metabolomic profiling using ultra-high performance liquid chromatography quadrupole electrostatic field orbitrap high-resolution mass spectrometer(UPLC-quadrupole-orbitrap MS)in 30 pairs of serum(15 PTC and 15 PTMC,30 controls),and the concentrations of differential metabolites were quantified using ultra-high performance liquid chromatography triple quadrupole tandem mass spectrometer(UPLC-MS/MS)in 200 pairs of sera(155 PTC and 45 PTMC,200 controls).3.Statistical analysis:The endogenous differential metabolites were screened using SIMCA-P 13.0.The KEGG database was used to analyze the metabolic pathways involved in the metabolites.Using SPSS 22.0,the association of metabolites with indices of thyroid function and thyroid antibodies was analyzed and the association of endogenous metabolites and PTC incidence risk was analyzed,as well as joint indicator for PTC diagnosis was constructed.Medcalc 19.5.6 software was used to perform receiver operating characteristic(ROC)curve analysis to compare the diagnostic values of metabolites for PTC.Results1.The proportion of smokers(20.0%),iodized salt consumption(100.0%)was higher in the case group than in the control group(16.7%,86.7%),and the proportion of drinkers(9.0%)was lower than in the control group(12.0%)(P<0.05).2.In the untargeted metabolomics study,42 endogenous differential metabolites were selected,including progesterone,estrone,androsterone glucuronide,Dtryptophan,hypoxanthine and L-arginine,which are mainly related to steroid hormone biosynthesis,tryptophan metabolism,purine metabolism and arginine biosynthesis(P<0.05).3.Compared with the control population,serum levels of D-tryptophan and estrone were increased and D-α-tocopherol was decreased in the total case patients,PTC patients and PTMC patients.Serum L-arginine level was increased in total case patients and PTC patients(P<0.05).4.D-tryptophan was positively correlated with TT3 and FT3,while estrone was negatively correlated with TT4 and FT4 and D-α-tocopherol and progesterone were negatively correlated with FT3,respectively,and β-Estradiol was negatively correlated with TgAb.However,the above correlations were all weak(P<0.05).5.L-arginine,D-tryptophan and estrone were found to be positively associated with the risk of total PTC and D-α-tocopherol was found to be negatively associated with the risk of total case.Further stratified analysis by pathological type,D-tryptophan was found to be positively associated with the risk of PTC and androsterone was found to be negatively associated with the risk of PTC(P<0.05).6.The area under the curve(AUC)of joint indicator combined by D-tryptophan,estrone,D-α-tocopherol,5 thyroid function indicators and 2 thyroid antibodies indicators was 0.875(P<0.05).Conclusions1.Smoking is a risk factor for PTC,and drinking is negatively correlated with the risk of PTC.2.D-tryptophan,estrone,D-α-tocopherol,progesterone and β-Estradiol show some correlation with thyroid hormones and thyroid antibody.3.Elevated D-tryptophan and estrone,and decreased D-α-tocopherol can increase the risk of PTC.4.The joint indicator that serum D-tryptophan,estrone,D-α-tocopherol combined with 5 thyroid function indicators and 2 thyroid antibodies indicators can improve the diagnostic efficacy of PTC,and its sensitivity and specificity are improved by approximately 19%and 30%,respectively,compared with single indicator,and it has a certain value in aiding the diagnosis of PTC.5.Steroid hormone biosynthesis,tryptophan metabolism,purine metabolism,arginine biosynthesis and vitamin E are initially identified as pathological biochemical mechanisms affecting the development and progression of PTC from population metabolomics. |
PDF Full Text Request