TRANSCRIPTOMIC ANALYSIS OF TOLL-LIKE RECEPTOR 4-REGULATED GENES REVEALED A THYROID CANCER MOLECULAR SIGNATURE

Buenos Aires

Congreso; XVII Latin American Thyroid Congress; 2019

Sociedad Latinoamericana de Tiroides

Introduction: Emerging evidence suggests that exacerbated Toll-like receptors (TLRs) signaling promotes tumor survival signals,thus favoring tumor progression. Recently, we evidenced functional TLR4 overexpression in well-differentiated thyroid carcinomas, asthe exogenous TLR4-agonist lipopolysaccharide trigger NF-κB signaling. Objectives: Molecular testing has improved the diagnosticof indeterminate thyroid nodules. We focused on TLR4-regulated genes to develop a thyroid cancer molecular signature. Methods:Transcriptomic analysis of TLR4-regulated differentially expressed genes was based on microarray and RNA-Seq datasets available inpublic domains (Gene Expression Omnibus, The Cancer Genome Atlas). Results: We uncover a putative TLR4-regulated molecularsignature highly expressed in papillary thyroid carcinomas. The diagnostic performance of the molecular signature for the diagnosis ofpapillary thyroid cancer was evaluated through ROC curves evidencing a sensitivity of 89%, specificity of 96%, positive predictive valueof 96%, and negative predictive value of 89%. Interestingly, the diagnostic value improves when only BRAF-like papillary thyroid tumorsare evaluated. These results will be discussed in the context of different commercially available molecular tests based on differential geneexpression. Conclusion: We uncovered a TLR4-regulated molecular signature overexpressed in papillary thyroid carcinomas. Althoughit promises to have an excellent diagnostic performance to detect papillary thyroid cancer, a clinical validation remains necessary in orderto be applied to the differential diagnosis of indeterminate thyroid nodules