title: Genomic evidence of reactive oxygen species elevation in papillary thyroid carcinoma with Hashimoto thyroiditis.
abstract: Elevated levels of reactive oxygen species (ROS) have been proposed as a risk factor for the development of papillary thyroid carcinoma (PTC) in patients with Hashimoto thyroiditis (HT). However, it has yet to be proven that the total levels of ROS are sufficiently increased to contribute to carcinogenesis. We hypothesized that if the ROS levels were increased in HT, ROS-related genes would also be differently expressed in PTC with HT. To find differentially expressed genes (DEGs) we analyzed data from the Cancer Genomic Atlas, gene expression data from RNA sequencing: 33 from normal thyroid tissue, 232 from PTC without HT, and 60 from PTC with HT. We prepared 402 ROS-related genes from three gene sets by genomic database searching. We also analyzed a public microarray data to validate our results. Thirty-three ROS related genes were up-regulated in PTC with HT, whereas there were only nine genes in PTC without HT (Chi-square p-value < 0.001). Mean log2 fold changes of up-regulated genes was 0.562 in HT group and 0.252 in PTC without HT group (t-test p-value = 0.001). In microarray data analysis, 12 of 32 ROS-related genes showed the same differential expression pattern with statistical significance. In gene ontology analysis, up-regulated ROS-related genes were related with ROS metabolism and apoptosis. Immune function-related and carcinogenesis-related gene sets were enriched only in HT group in Gene Set Enrichment Analysis. Our results suggested that ROS levels may be increased in PTC with HT. Increased levels of ROS may contribute to PTC development in patients with HT.
authors.affiliation: Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Yi
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Park
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Sung
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Kwak
authors.forename: Jihan
authors.initials: J
authors.lastname: Yu
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Chang
authors.forename: Jo-Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Ha
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Paik
authors.forename: Woo Seung
authors.initials: WS
authors.lastname: Lee
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D002277:Carcinoma / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D030562:Databases, Protein; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D023281:Genomics / Q000379:methods; D050031:Hashimoto Disease / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D020407:Internet; D008297:Male; D040901:Proteomics / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism*; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D015854:Up-Regulation
chemical_list: D017382:Reactive Oxygen Species