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Background  The prognostic variability of thyroid carcinomas has led to the search for accurate biomarkers at the molecular level. Follicular thyroid carcinoma (FTC) is a typical example of differentiated thyroid carcinomas (DTC) in which challenges are faced in the differential diagnosis.    Methods  We used high-throughput paired-end RNA sequencing technology to study four cases of FTC with different degree of capsular invasion: two minimally invasive (mFTC) and two widely invasive FTC (wFTC). We searched by genes differentially expressed between mFTC and wFTC, in an attempt to find biomarkers of thyroid cancer diagnosis and/or progression. Selected biomarkers were validated by real-time quantitative PCR in 137 frozen thyroid samples and in an independent dataset (TCGA), evaluating the diagnostic and the prognostic performance of the candidate biomarkers.    Results  We identified 17 genes significantly differentially expressed between mFTC and wFTC.  C1QL1 ,  LCN2 ,  CRABP1  and  CILP  were differentially expressed in DTC in comparison with normal thyroid tissues.  LCN2  and  CRABP1  were also differentially expressed in DTC when compared with follicular thyroid adenoma. Additionally, overexpression of  LCN2  and  C1QL1  were found to be independent predictors of extrathyroidal extension in DTC.    Conclusions  We conclude that the underexpression of  CRABP1  and the overexpression of  LCN2  may be useful diagnostic biomarkers in thyroid tumours with questionable malignity, and the overexpression of  LCN2  and  C1QL1  may be useful for prognostic purposes.    Electronic supplementary material  The online version of this article (10.1186/s12885-017-3948-3) contains supplementary material, which is available to authorized users.

CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension