| Objective: The expression levels of Midkine(Midkine)and its ratios in fine-needle aspirates of benign and malignant thyroid nodules were detected to evaluate the role of these concentrations in predicting thyroid malignancy.Methods: This retrospective study included 217 patients with 242 thyroid nodules who underwent preoperative fine-needle aspiration biopsy(FNAB)and/or thyroidectomy between April and September of 2017.The expression levels of Midkine in fine-needle aspirates were measured by enzyme-linked immunosorbent assay(ELISA),the expression levels of thyroglobulin(TG)and free thyroxine 4(FT4)in fine-needle aspirates were measured by chemiluminescent immunometric assays.According to the Bethesda Report Thyroid Cytopathology System(TBSRTC)and the Thyroid Imaging Report and Data System(TI-RADS)issued by the American College of Radiology(ACR),fine-needle aspiration cytology(FNAC)results and ultrasound results of thyroid nodules were classified.The relationship between each indicator and clinical pathological characteristics were analyzed and the receiver operating characteristic curve(ROC)curve were used to further investigate the sensitivity,specificity and accuracy of indicators,ultrasound and FNAC.Results:1.According to the pathological results,the different expression level of Midkine-related ratios in thyroid benign and malignant nodules were analyzed.The expression levels of MK/TG and MK/FT4 in papillary thyroid carcinoma were significantly higher than those in benign thyroid nodules(P<0.05),while the expression levels of TG,FT4 and FT4/MK in PTC decreased(P<0.05)2.The expression levels of MK/TG and MK/FT4 both increased in PTC with the maximum tumor diameters of 1-2cm and 2-4cm(P = 0.009,P = 0.001),and the expression levels of both were also increased in PTC that they invaded through the capsule and reached the outside and invaded to perithyroidal soft tissues or strap muscles(P = 0.001,P = 0.003);In addition,the expression of MK/TG increased with the increase of T stage(P = 0.002),and MK/FT4 also had a different expression in T stage(P = 0.002);However,only the expression level of MK/FT4 increased in the N1 stage(P = 0.025).3.According to the ROC curve results,the diagnostic accuracy of each indicator for benign and malignant thyroid nodules was evaluated.The area under the curve(AUC)of MK/TG was 0.719 with the cutoff value of 55.57ng/mg,while the AUC of MK/FT4 is 0.677 with the cutoff value of 0.11μg/pmol.There was no statistical difference between the two AUCs(P = 0.91).The sensitivity,specificity,and accuracy of MK/TG were 58%,87%,and 62%,respectively.The sensitivity,specificity,and accuracy of MK/FT4 were 44%,91%,and 50%,respectively.Although the sensitivity and accuracy were higher in MK/TG than in MK/FT4,the specificity of MK/FT4 was better than MK/TG.4.Investigate the value of Midkine ratios as a supplementary diagnostic method of FNAC.Midkine and its ratios were differentially expressed in the five FNA categories(P <0.05),mainly due to FNA II and VI specimens.FNAC in combination with MK/FT4 had a higher sensitivity(95% vs.91%)and accuracy(96% vs.92%)than FNAC alone for FNA I,III,and V specimens.FNAC combined with MK/TG did not improve the diagnostic efficiency of FNAC.5.Analyze whether Midkine ratios can be used as a supplementary diagnostic method for ultrasound.Compared with ACR TI-RADS alone,both MK/TG and MK/FT4 combining with ACR TI-RADS showed higher sensitivities(91% vs83%,89% vs 83%)and accuracies(88% vs.83%,87% vs 83%),but lower specificities(65% vs.74%,70% vs 74%).Conclusion:1.Both MK/FT4 and MK/TG had good diagnostic efficiency for PTC,and can be considered as potentially new tumor markers for the diagnosis of PTC.2.For FNA I,III and V,cytologically indeterminate thyroid nodules,MK/FT4 may be a better supplementary diagnostic method for preoperative FNAC than MK/TG.3.Both MK/FT4 and MK/TG can be used as a supplementary diagnostic method for preoperative ultrasound. |
PDF Full Text Request