Integrative Methylome and Transcriptome Characterization Identifies SERINC2 as a Tumor-Driven Gene for Papillary Thyroid Carcinoma.

Simple Summary: Papillary thyroid carcinoma is still the most common endocrine tumor, most of which can be diagnosed by pathological results. However, there is still a small number of cases that are difficult to judge malignancy. In this study, we performed an integrative analysis of DNA methylation and RNA array from our cohort for potential papillary thyroid cancer-specific indicators. SERINC2, one of the differentially methylated and expressed genes, was first identified as a potential tumor-driven indicator in papillary thyroid carcinoma. We confirmed the influence of SERINC2 on proliferation and apoptosis in vitro after intervention or overexpression. Furthermore, we found tryptophan metabolism as a potential pathway targeted by SERINC2 through the investigation of data from the Cancer Dependency Map. In conclusion, our results demonstrate the whole-genome DNA methylation and gene expression profiles of papillary thyroid carcinoma, identify a new tumor-driven indicator, and provide a novel insight into the etiology of papillary thyroid cancer. Most papillary thyroid carcinomas (PTCs) can be diagnosed preoperatively by routine evaluation, such as thyroid ultrasonography and fine-needle aspiration biopsy. Nevertheless, understanding how to differentiate indolent thyroid tumors from aggressive thyroid cancers remains a challenge, which may cause overtreatment. This study aimed to identify papillary thyroid cancer-specific indicators with whole-genome DNA methylation and gene expression profiles utilizing Infinium Methylation EPIC BeadChip (850k) and RNA arrays. In this paper, we report SERINC2 as a potential tumor-driven indicator in PTC. The up-regulated expression levels of SERINC2 were verified in PTC cell lines via qPCR. Then, cell counting kit 8 (CCK-8), wound healing, and flow cytometric assays were performed to confirm the influence of SERINC2 on proliferation and apoptosis in PTC cell lines after intervention or overexpression. Moreover, the investigation of data from the Cancer Dependency Map (DepMap) provided a potential pathway targeted by SERINC2. The activation of the tryptophan metabolic pathway may reduce the dependency of SERINC2 in thyroid cancers. In conclusion, our results demonstrate the whole-genome DNA methylation and gene expression profiles of papillary thyroid carcinoma, identify SERINC2 as a potential tumor-driven biomarker, and preliminarily verify its function in PTC. [ABSTRACT FROM AUTHOR]