Preliminary Study on the Sequencing of Whole Genomic Methylation and Transcriptome-Related Genes in Thyroid Carcinoma

SIMPLE SUMMARY: Epigenetic alterations are critical for tumor onset and development. DNA methylation is one of the most studied pathways concerning various types of cancer. A promising and exciting avenue of research is the discovery of biomarkers of early-stage malignancies for disease prevention and prognostic indicators following cancer treatment by examining the DNA methylation modification of relevant genes implicated in cancer development. We have made significant advances in the study of DNA methylation and thyroid cancer. This study is novel in that it distinguished methylation changes that occurred primarily in the gene body region of the aforementioned hypermethylated or hypomethylated thyroid cancer genes. Our findings imply that exposing whole-genome DNA methylation patterns and gene expression profiles in thyroid cancer provides new insight into the carcinogenesis of thyroid cancer, demonstrating that gene expression mediated by DNA methylation modifications may play a significant role in tumor growth. ABSTRACT: Thyroid carcinoma is the most prevalent endocrine cancer globally and the primary cause of cancer-related mortality. Epigenetic modifications are progressively being linked to metastasis. This study aimed to examine whole-genome DNA methylation patterns and the gene expression profiles in thyroid cancer tissue samples using a MethylationEPIC BeadChip (850K), RNA sequencing, and a targeted bisulfite sequencing assay. The results of the Illumina Infinium human methylation kit (850K) analyses identified differentially methylated CpG locations (DMPs) and differentially methylated CpG regions (DMRs) encompassing nearly the entire genome with high 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 that were up-regulated and 453 of which that were down-regulated. The targeted bisulfite sequencing assay revealed that CHST2, DPP4, DUSP6, ITGA2, SLC1A5, TIAM1, TNIK, and ABTB2 methylation levels were dramatically lowered in thyroid cancer patients when compared to the controls, but GALNTL6, HTR7, SPOCD1, and GRM5 methylation levels were significantly raised. Our study revealed that the whole-genome DNA methylation patterns and gene expression profiles in thyroid cancer shed new light on the tumorigenesis of thyroid cancer.