TRANSCRIPTOMIC-BASED MASTER REGULATORS SCREENING IN PAPILLARY THYROID CARCINOMA

Buenos Aires

Congreso; XVII Latin American Thyroid Congress; 2019

Sociedad Latinoamericana de Tiroides

Introduction: Gene expression profile in a cellular context is the reflection of specific regulatory programs. A small number ofmaster regulator-acting transcription factors coordinate tumor phenotype. Interestingly, master regulators are increasingly emerging asoptimal biomarkers and therapeutic targets. Objectives: To uncover master regulators, whose aberrant activity is both necessary andsufficient to maintain the biological phenotype of papillary thyroid carcinoma. Methods: RNA-seq data was obtained from The CancerGenome Atlas. Differential gene expression was computed using DEseq2. Transcription factor-centered networks were inferred usingARACNe-AP algorithm. Master Regulators were inferred using VIPER analysis. Results: We generated a papillary thyroid carcinomaspecific transcription factor-centered gene regulatory network. Master regulator analysis considering differential gene expression intumor and paired-normal samples revealed several master regulator-putative transcription factors in BRAF and RAS-like papillarythyroid tumors. Master regulators driving BRAF and RAS-like tumor phenotypes do not overlap. Significantly, we identified severalmaster regulators ? GATAD2A, ETV5, and PROX1 ? previously involved in thyroid carcinogenesis. Moreover, we evidenced masterregulators connected to a regulon controlling NF-κB signal pathway. Conclusion: Using high-throughput transcriptomic data, weuncovered a set of master regulator-acting transcription factors that differentially coordinate BRAF and RAS-like papillary thyroidtumor phenotype. A comprehensive understanding of master regulators-promoting thyroid cancer will provide novel diagnostic andtherapeutic applications.