| Objective To analyze serum metabolic characteristics between patients with PTC and volunteers under the condition of different iodine intake and to explore the development of PTC from the perspective of metabolomics.Methods 1.Based on the inclusive and exclusive criteria of PTC group,preoperative serum samples and preoperative urine samples from PTC patients were collected in the department of thyroid surgery at the Fujian Medical University Union Hospital from September 2017 to June 2018.Meanwhile,serum samples and urine samples of volunteers were collected according to the inclusive and exclusive criteria of control group.All serum samples were stored at-80℃ and urine serum were stored at-20℃.2.Urinary iodine concentration was measured in all urine samples using the quantitative test kit(100-300ug/L,300-1200μg/L,Conson Biochemicals Co Ltd,Wuhan,China)by As3+-Ce4+ catalytic spectrophotometry under 400 nm and 380 nm respectively according to the manufacturer’s protocol.Then the data of UIC was processed with IBM SPSS 25.0 and the patients and volunteers according to different levels of UIC were divided into different groups including insufficient(H1and P1),adequate(H2 and P2),above requirement(H3 and P3),excessive(H4 and P4))respectively.3.All serum samples were analyzed by the Bruker 500 Hz 1H-nuclear magnetic resonance(1H-NMR)spectroscopy and the NMR spectra were recorded.4.The FID signals of each 1H-NMR spectrum were performed Fourier transform(FT),manually phased and baseline corrected and adjusted by an internal reference of alanine at 1.47 ppm was set to 0.00 ppm with Bruker Biospin software(Bruker,Germany).Spectrum binning was operated on all 1 H-NMR data with a bin width of 0.04 ppm from 0.1 ppm to 10.00 ppm.5.The obtained dataset was normalized to the total spectrum and scaled to the unit variance.Then,the normalized integral values from serum samples were imported into “R”(http://cran.r-project.org/)which is a freely available open-source software package for multivariate pattern recognition analysis including PCA and PLS-DA.Additionally,data visualization was operated by the “ggplot2” package.Aim to study the endogenous serum metabolic difference between PTC group and control group with different iodine intake.Results 1.In this study,72 patients including 7 of group P1,19 of group P2,22 of group P3 and 24 of group P4 respectively and 56 volunteers involving 14 of group H1,23 of group H2,10 of group H3 and 9 of group H4 respectively were recruited.There was no significance(p>0.05)in sex and age among 4 subgroups from group P and group H involving P1 and H1,P2 and H2,P3 and H3 as well as P4 and H4 and among intragroup analysis of group P and group H respectively.2.The mean ± standard(M±SD)of UIC among group P1,group P2,group P3 and group P4 were 67.44 ± 16.76 μg/l,157.12 ± 23.63 μg/l,256.41 ± 29.98 μg/l and 367.76 ± 36.77 μg/l respectively and among group H1,group H2,group H3 and group H4 were 72.56 ± 24.89 μg/l,154.17 ± 29.47 μg/l,241.85 ± 20.73 μg/l and 385.77 ± 69.53 μg/l respectively.There was no statistical difference(p>0.05)concerning the values of UIC between group P and group H at the same UIC level.However,the population distribution of UIC between PTC patients and volunteers was different.The average UIC of group P was higher than that of group H.The urine iodine concentration of group P was mainly in the above requirement level(200 μg/l≤UIC≤299 μg/l)and excessive level(UIC≥300 μg/l),while the UIC of group H was mainly in the adequate level(100 μg/l≤UIC≤199 μg/l).3.Compared with group H,group P had a lower level of tau-Methyl histidine,glucose,glycine,methanol,betaine,creatinine,glutamine,methionine,arginine and isoleucine but a higher level of gluconate,acetone and lactate.4.The concentrations of tau-Methyl histidine,serine,glucose,glycine,methanol,betaine,creatine,glutamine and methionine were decreased but valine,acetone and lactate were increased in group P1 Compared with group H1.5.As compared with group H2,group P2 had a lower level of glucose,glycine,methanol,betaine,creatine,citrate,glutamine,arginine and leucine but a higher level of valine and acetone.6.Compared with group H3,group P3 had a reduced level of glucose,methanol,betaine,glutamine,arginine,valine and isoleucine but a raising level of gluconate,lactate,creatinine and serine.7.There was no significant metabolites(R2<0.5)in group P4 analyzed by PLS-DA at ecessive level compared with group H4.Conclusion 1.The iodine intake of PTC patients was higher than general people.The population of PTC was mainly distributed in the level of more adequate iodine intake and excessive iodine intake.Conversely,the general people were mainly distributed in the level of adequate iodine intake.2.PTC patients with inadequate iodine intake,adequate iodine intake and above requirement iodine intake had the enhanced glucose metabolism,lipid metabolism concerning betaine metabolism and glutamine metabolism as the common serum metabolic characteristics.3.There was a metabolic significance involving nucleotide metabolism,amino acid metabolism and creatine metabolism among PTC patients with inadequate,adequate and above requirement iodine intake.4.There was no statistical difference between PTC group and control group with excessive iodine intake,which might be resulted from a small and insufficient sample.5.The different metabolic characteristics in PTC patient with different iodine intake compared with control group suggested that iodine intake might have an influence on the development of PTC. |
