Abstract 5020: Identification of transcriptional regulatory networks associated with papillary thyroid carcinoma

Abstract

Abstract Background: Identification of critical transcription factors (TFs) required by cancer cells to sustain biological processes that support their growth and survival is urgently needed to develop strategies targeting them. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy making about 80% of all thyroid cancers cases. Gene expression of a number of thyroid-specific TFs has been found deregulated in thyroid carcinomas. Therefore, molecular approaches targeting overexpressed oncogenes are desirable therapeutic methods to improve the treatment of cancer patients. In this study, we used Transcription Factor Enrichment Analysis (TFEA) to detect positional motif enrichment associated with changes in transcription observed in this cancer type. Methods: We previously identified differentially expressed genes between PTC and normal thyroid tissue using DNA microarrays. In the current study, the former overexpressed genes were subjected to TFEA using the web-based tool ChEA3. For comparison purposes, the Gene Expression Profiling Interactive Analysis (GEPIA2) tool was used to identify the most differentially overexpressed genes in thyroid carcinoma versus paired normal samples from patients in the TCGA database, and the differentially overexpressed gene set was also subjected to TFEA. Results: TFEA using the ChEA3 web-server identified several TFs associated with overexpressed genes observed in PTC. The top-ranked TFs found in both the gene set identified in PTC patient samples using microarrays and the gene set identified in the TCGA database using GEPIA2 were: EHF, POU2F3, KLF5, ELF3, HES2, GRHL3, and HNF1B. Several of these TFs have previously been identified in thyroid carcinomas, while others are newly identified. EHF and ELF3 are known to be overexpressed in thyroid carcinogenesis; KLF5 is a zinc-finger transcriptional factor recently found to be highly expressed in a subset of PTC patients with aggressive behavior. Bioinformatics analysis has previously shown that HNF1B is up-regulated in several cancers including thyroid carcinomas. The role of the remaining identified TFs in thyroid carcinogenesis has not been described. POU2F3 is a member of the POU domain family of transcription factors that bind to a specific octamer DNA motif and regulate cell type-specific differentiation pathways. Hes2 encodes a mammalian basic helix-loop-helix transcriptional repressor. GRHL3 (Grainyhead-like 3) is a transcription factor involved in epithelial morphogenesis. Conclusions: Bioinformatics analysis of differentially expressed genes in tumor versus normal paired thyroid tissue samples from PTC patients and in thyroid carcinoma versus paired normal samples from patients in the TCGA database allowed the identification of TFs that may play a role in PTC. The group of TFs identified in this study may represent potential therapeutic targets for this cancer type. Citation Format: Niradiz Reyes, Stephanie Figueroa, Christian Figueroa, Jan Geliebter. Identification of transcriptional regulatory networks associated with papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5020.