Transcriptomic analysis of Toll-like receptor 4-regulated genes revealed a thyroid cancer molecular signature

MIRANDA, L; MARTI, MA; GEYSELS, RC; NICOLA, JP

Buenos Aires

Congreso; XVII Latin American Thyroid Society Congress; 2019

Latin American Thyroid Society

Emergingevidence suggests that exacerbated Toll like receptors (TLRs) signalingpromotes tumor survival signals, thus favoring tumor progression. Recently, we evidencedfunctional TLR4 overexpression in well-differentiated thyroid carcinomas, as theexogenous TLR4-agonist lipopolysaccharide trigger NF-κB signaling.Moleculartesting has improved the diagnostic of indeterminate thyroid nodules. Wefocused on TLR4-regulated genes to develop a thyroid cancer molecularsignature.Transcriptomic analysis of TLR4-regulateddifferentially expressed genes was based on microarrayand RNA-Seq datasets available in public domains (Gene Expression Omnibus, TheCancer Genome Atlas).We uncover a putative TLR4-regulatedmolecular signature highly expressed in papillary thyroid carcinomas. Thediagnostic performance of the molecular signature for the diagnosis ofpapillary thyroid cancer was evaluated through ROC curves evidencing a sensitivityof 89%, specificity of 96%, positive predictive value of 96%, and negativepredictive value of 89%. Interestingly, the diagnostic value improves when onlyBRAF-like papillary thyroid tumors are evaluated. Theseresults will be discussed in the context of different commercially availablemolecular tests based on differential gene expression.We uncovered a TLR4-regulated molecularsignature overexpressed in papillary thyroid carcinomas. Although it promisesto have an excellent diagnostic performance to detect papillary thyroid cancer,a clinical validation remains necessary in order to be applied to the differentialdiagnosis of indeterminate thyroid nodules.