| BackgroundDNA methylation,the most widely studied epigenetic process regulating gene expression,has been implicated in the aetiology of a variety of complex diseases and characteristics,including thyroid cancer.DNA methylation has been shown to suppress gene expression through imprinting,X-chromosome inactivation,and retrotransposon silencing.However,the significance of DNA methylation in suppressing gene expression is not entirely known outside of these contexts.This is especially relevant in disorders like cancer,in which normal DNA methylation patterns are significantly altered.In thyroid cancer,as well as nearly all other kinds of cancer,the majority of the genome loses methylation while small regions gain methylation.When DNA methylation occurs at a gene promoter,it often results in decreased gene expression.As a result,these hypo-and hypermethylated regions may contribute to the development and progression of cancer by activating oncogenes and silencing tumour suppressor genes.Thyroid carcinoma represents only 2% of all malignant diseases,it is the most common endocrine system malignancy.Thyroid papillary carcinoma(PTC),thyroid follicular carcinoma(FTC),undifferentiated thyroid carcinoma(ATC)and thyroid medullary carcinoma(MTC)are the main pathologic types of primary thyroid carcinoma.Thyroid papillary carcinoma is the most common pathological type,accounting for about 80% of thyroid cancer.Although the pathogenesis of thyroid cancer in recent years has made great progress,but the epigenetic and its specific mechanism of the disease is still unclear.ObjectiveThe aim of the present study was to examine patterns of whole genomic DNA methylation and profile of gene expressions in thyroid cancer.Also,Compare and evaluate the diagnostic capabilities of preoperative ultrasonography(US)and magnetic resonance imaging(MRI)in the cervical lymph nodes of patients with papillary thyroid cancer.MethodsWe have collected a total of 86 matched samples of pathologically verified postoperative malignant carcinoma and normal thyroid tissues from 43 pairs of specimens from patients who underwent thyroidectomy at the Zhenjiang First People’s Hospital Affiliated with the Institute of Jiangsu University between July 2018 & September 2020.Thyroid cancer tissue samples were used in Methylation Epic bead chip(850k),RNA sequencing and targeted bisulfite sequencing assay were estimated.Between January 2017 and January 2021,156 patients,who had undergone thyroidectomy and preoperative US and MRI,were selected.At least 4 radiologists unilaterally and spontaneously investigated the US and MRI attributes of the cervical lymph nodes.The efficiency of diagnostic imaging for cervical lymph nodes,including their true-positive rate or sensitivity,true-negative rate or specificity,positive predictive value,negative predictive value,and predictive accuracy were assessed.ResultsThe results of Illumina Infinium human methylation(850k)analyses identified differentially methylated Cp G locations(DMP)and differentially methylated Cp G regions(DMR)encompassing nearly the whole genome with appropriate resolution and depth.Gene ontology and KEGG pathway analyses revealed that the genes associated with DMRs belonged to various domain-specific ontologies,including cell adhesion molecule binding and proliferation.The RNA-Seq study found 1627 differentially expressed genes,1174 of which were up-regulated and 453 of which were down-regulated.Additionally,the targeted bisulfite sequencing for gene expression CHST2,DPP4,DUSP6,ITGA2,SLC1A5,TIAM1,TNIK,and ABTB2 methylation levels were dramatically lowered in thyroid cancer patients compared to controls,but GALNTL6,HTR7,SPOCD1,CDH16 and GRM5 methylation levels were significantly raised.In the assessment of cervical lymph node metastases of papillary thyroid cancer,diagnostic sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of diagnostic US vs.MRI were 58.0% vs.79.7%,69.0% vs.83.9%,59.7% vs.79.7%,67.4% vs.83.9%,and 64.1% vs.82.1%,respectively.The accuracy consistency of the two was 83.5%.ConclusionsThe revelation of whole genomic DNA methylation patterns & profiles of gene expression in thyroid cancer sheds new light on the tumorigenesis of thyroid cancer,indicating that gene expression regulated by DNA methylation alterations may play a critical role in tumor progression.MRI is more effective than US in diagnosing and assessing cervical lymph node metastases of papillary thyroid cancer. |
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