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Papillary thyroid carcinoma (PTC) is the most common malignant tumor of endocrine systems. Chromosomal instability (CIN) is crucial to the clinical prognoses of tumor patients. DNA methylation plays an important role in the regulation of gene expression and CIN. Based on PTC samples from The Cancer Genome Atlas database, we used multiple regression analyses to identify methylation patterns of CpG sites with the strongest correlation with gene expression. A total of 4,997 genes were obtained through combining the CpG sites, which were represented as featured DNA methylation patterns. In order to identify CIN-related epigenetic markers of PTC survival, we developed a method to characterize CIN based on DNA methylation patterns of genes using the Student’s t statistics. We found that 1,239 genes were highly associated with CIN. With the use of the log-rank test, univariate Cox regression analyses, and the Kaplan-Meier method, DNA methylation patterns of UBAC2 and ELOVL2, highly correlated with CIN, provided potential prognostic values for PTC. The higher these two genes, risk scores were correlated with worse PTC patient prognoses. Moreover, the ELOVL2 risk score was significantly different in the four stages of PTC, suggesting that it was related to the progress of PTC. The DNA methylation pattern associated with CIN may therefore be a good predictor of PTC survival. Keywords: papillary thyroid carcinoma, chromosomal instability, DNA methylation, gene expression, prognosis

Yanmeizhi Wu,1 Jun Han,1 Kazakova Elena Vladimirovna,1 Shumei Zhang,2 Wenhua Lv,2 Yan Zhang,3 Esma Jamaspishvili,1 Jingxue Sun,1 Qingxiao Fang,1 Jingjing Meng,1 Hong Qiao1 1Department of Endocrinology, No.2 Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Department of Epigenetics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 3Department of Bioinformatics and Computational Epigenetics, College of Life and Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Hong QiaoDepartment of Endocrinology, No.2 Affiliated Hospital of Harbin Medical University, No. 148 Baojian Road, Nangang District, Harbin, Heilongjiang Province, People’s Republic of ChinaTel +86 13945677355Email qhong0823@163.comIntroduction: PTC is not generally considered a lethal disease, but prone to recurrence as the prognosis. Hashimoto’s thyroiditis (HT) is an important factor that affects the prognosis of papillary thyroid carcinoma (PTC). It is crucial to find biomarkers to identify the combination of HT with PTC and to predict the prognosis.Methods: RNASeq data from the Cancer Genome Atlas (TCGA) database was used to screen differentially expressed genes (DEGs) of PTC with HT via the edgeR package of R software version 3.3.0. Also, the DEGs were applied to the DAVID web-based tool to determine the enrichment of gene functions via Gene Ontology (GO) analysis and to identify associated pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. By constructing protein interaction networks within Cytoscape software, we screened candidate genes and explored possible relationships with the clinical phenotype of PTC. Finally, additional thyroid tissue samples were collected to verify the results above.Results: After analyzing the RNA-Seq data of PTC patients from the Cancer Genomic Atlas, 497 differentially expressed PTC genes were found to be associated with HT, of which protein tyrosine phosphatase receptor type C (PTPRC), KIT, and COL1A1 were associated with tumor size and lymph node metastasis (p < 0.05). Verification of these results with another 30 thyroid tissues of clinical PTC patients revealed that the expression level of PTPRC in the PTC with HT group was higher than that in the PTC without HT group (p < 0.05) and the ROC curve showed a good discrimination (area under the curve = 0.846). However, the correlation with the clinical phenotype was not statistically significant (p > 0.05).Discussion: These data suggest that upregulation of PTPRC enhances the incidence of HT associated with PTC and is also predictive of a poor prognosis.Keywords: papillary thyroid carcinoma, Hashimoto’s thyroiditis, PTPRC, biomarker, prognosis

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