Abstract
BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.
Highlights
The prognostic variability of thyroid carcinomas has led to the search for accurate biomarkers at the molecular level
Gain of C1QL1 and LCN2 expression, and loss of IL22RA1, MAMDC2, CILP, ASXL3, CRABP1, and SCUBE3 expression were confirmed in widely invasive FTC (wFTC) compared with minimally invasive FTC (mFTC) and between the four Follicular thyroid carcinoma (FTC) and their respective corresponding normal thyroid tissue (Additional file 4: figure S1)
Based on the accuracy of gene expression levels obtained from paired-end RNA sequencing (RNA-seq) and quantitative PCR (qPCR) in the FTC and in the gene expression levels in their normal thyroid tissues by qPCR, C1QL1, LCN2, CRABP1 and CILP genes were selected to be tested as biomarkers in a well-characterized series of differentiated thyroid carcinoma (DTC) (Table 1)
Summary
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. More than 95% of thyroid cancer cases originate from follicular epithelial cells [3]. Despite the overall good prognosis of these two main histotypes of differentiated thyroid carcinoma (DTC) [1], some cases. The increasing incidence of thyroid cancer has led to the search for good biomarkers that can help in the diagnosis of malignancy and/or predict the clinical behaviour of the tumours. Clinical and histopathological prognostic factors remain the only robust elements to be used for diagnosis and prognosis of patients with thyroid tumours [4], new markers are revealing some diagnostic or prognostic value per se.
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