| BACKGROUND:Hashimoto thyroiditis(HT),also known as chronic lymphocytic thyroiditis,is the most common autoimmune thyroid disease frequently causing hypothyroidism.It is characterized by the presence of thyroid-specific autoantibodies and infiltration of the thyroid gland by inflammatory cells.HT has a long-term course and its clinical manifestation is exceedingly complicated.Besides,it is likely that HT could co-exist with thyroid carcinoma(HT-TC).When HT is accompanied with thyroid cancer,there are no other symptoms,which makes it hard to diagnose.In addition,little is known about the genomic features and mutation profiles of HT-TC.AIMS:The protein-coding regions of HT-TC were interrogated by whole exome sequencing(WES).The purpose of our study is to elucidate the etiology,biological behaviors of HT-TC and to differentiate it with common thyroid carcinoma.METHODS:Fresh-frozen tumors and matched normal blood from 6 patients were collected from Department of Head and Neck Surgery of Cancer Institute/Hospital,Chinese Academy of Medical Sciences.The histology of all cases was papillary subtype.Based on the workflow of WES,we carried out the extraction of gDNA,construction of DNA library,captures of exonic region and sequencing.Sequencing data were preprocessed with GATK Best Practice pipeline and somatic SNVs(single nucleotide variations)and Indels(insertions and deletions)were identified with MuTect and Strelka,respectively.Somatic mutations of 492 papillary thyroid carcinomas from The Cancer Genome Atlas(TCGA-PTC)project were downloaded and further analyzed.Genetic alterations of HT-TC and TCGA-PTC were compared.RESULTS:Our data suggested that mutation load of HT-TC was much lower than some common tumors,such as liver cancer and lung cancer.In all,44 somatic mutations were identified and 29 of them were non-silent in HT-TC.BRAF V600E hotspot mutation was recurrent in half of the carcinomas sequenced.FCGR2A,CRIPAK,FOXO3,NCOA3,PDE4DIP and BRD9 were also mutated in HT-TC.Moreover,HT-TC and TCGA-PTC shared some genetic features,for example BRAF V600E with similar mutation frequency and the predominant C>T transitions spectra.Nevertheless,there was a modest discrepancy in the mutation spectra of these two tumor types.CONCLUSIONS:We identified genetic features of HT-TC using genome-wide approach.The somatic alterations of HT-TC suggest its genetically distinct features compared with common papillary thyroid carcinoma.These results provide new insight into the understanding of genetic profiles of HT-TC.These findings might be used to differentiate thyroid cancer patients with HT and those without.BACKGROUND:Esophageal cancer is a common type of gastrointestinal cancer.The pathological subtypes of esophageal cancer include squamous carcinoma and adenocarcinoma.In China,esophageal squamous cell carcinoma(ESCC)is the most prevalent type of esophageal cancer compared to adenocarcinoma in western countries.Surgery,chemotherapy,radiotherapy as well as other adjuvant therapies may play a part in the treatment of ESCC,but the therapeutic efficacy is not satisfactory and the survival differences exist among patients.The molecular targeted therapy is still on clinical trails and there is no targeted drug in daily clinical practice.As a result,it is necessary to study the molecular profiles of ESCC intensely.AIMS:To deeply investigate the gene expression profiles of ESCC from The Cancer Genome Atlas(TCGA)database and the relationship between gene expression and prognosis.METHODS:RNA-seq V2 data as well as corresponding clinical data of esophageal squamous cell carcinoma patients were downloaded from TCGA database.Differentially expressed genes were identified between normal and tumor samples using edgeR package.Gene function enrichment analyses of differentially expressed genes were conducted through DAVID and a protein-protein interaction network based on differentially expressed genes was constructed using STRING database.Gene co-expression network was created and hub genes of selected module were identified.Finally,patients were divided into two groups based on median gene expression level and survival analysis was performed using log-rank test.RESULTS:We downloaded RNA-Seq data and clinical data of 81 esophageal squamous cell carcinoma patients.Besides,RNA-seq V2 data of 11 normal samples were downloaded as well.In total,2788 genes were differentially expressed.1168 genes were up-regulated in tumor compared with normal samples and 1620 genes were down-regulated in tumor cases.Up-regulated genes were enriched in cell cycle,DNA replication and mismatch repair pathways,while down-regulated genes were enriched in some metabolic pathways.Genes,such as ANO1,FGF19 and NKX2-1 which are amplified in ESCC,were directly interacted with other critical genes through our protein-protein interaction network analysis.Ten co-expression modules were identified based on our gene co-expression network analysis and brown module was significantly correlated with tumor location(P=0.003).Hub genes of brown module were found,including RPS2?RPLPO?RPL6?RPL27?RPL41?RPL18A?RPS28?RPS9 and RPL19.The expression levels of TNFRSF10B and DDX18 were correlated with patients'prognosis.High expression levels of these two genes were associated with longer times of patient survival.The three-year survival rates were 82.5%and 15.1%in TNFRSF10B high and low expression level groups,respectively.Similarly,the three-year survival rates were 82.4%and 15.2%in DDX18 high and low expression level groups,respectively.CONCLUSIONS:The gene expression features of esophageal squamous cell carcinoma are deeply examined.Differentially expressed genes between normal and tumor tissues are identified.Protein-protein interaction network based on differentially expressed genes and gene co-expression network based on tumor gene expression profiles are constructed.The relationship between gene expression and prognosis is interrogated.Theses data could provide information for further functional experiments and may give clue to the prognosis assessment. |
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