Validity of multiplex biomarker model of 6 genes for the differential diagnosis of thyroid nodules

• Main Authors: Ducena Kristine, Ābols Arturs, Vilmanis Janis, Narbuts Zenons, Tārs Juris, Andrējeva Diana, Linē Aija, Pīrāgs Valdis
• Format: Article
• Language: English
• Published: BMC 2011-06-01
• Series: Thyroid Research
• Online Access: http://www.thyroidresearchjournal.com/content/4/1/11

<p>Abstract</p> <p>Background</p> <p>Currently the cytological examination of fine needle aspiration (FNA) biopsies is the standard technique for the pre-operative differential diagnosis of thyroid nodules. However, the results may be non-informative in ~20% of cases due to an inadequate sampling and the lack of highly specific, measurable cytological criteria, therefore ancillary biomarkers that could aid in these cases are clearly needed. The aim of our study was to evaluate the mRNA expression levels of 8 candidate marker genes as the diagnostic biomarkers for the discrimination of benign and malignant thyroid nodules and to find a combination of biomarkers with the highest diagnostic value.</p> <p>Materials and methods</p> <p>mRNA expression levels of eight candidate marker genes - <it>BIRC5, CCND1, CDH1, CITED1, DPP4, LGALS3, MET </it>and <it>TFF3 </it>was measured by real-time RT-PCR in paired nodular and surrounding normal thyroid tissue specimens of 105 consecutive patients undergoing thyroid surgery and compared between different types of thyroid lesions.</p> <p>Results</p> <p>Significant differences in the mRNA expression levels between the normal and malignant thyroid tissues and between benign and malignant nodules were found for <it>BIRC5, CCND1, CITED1, DPP4, LGALS3, MET </it>and <it>TFF3</it>, but not <it>CDH1</it>. On a single gene basis, relative quantity (RQ) of <it>LGALS3 </it>had the highest diagnostic value for the discrimination of malignant and benign thyroid nodules (AUC = 0.832, P < 0.0001 and 90.9% sensitivity and 65.6% specificity at the optimal cut-off on ROC curve). The only two-marker set that outperformed <it>LGALS3 </it>was RQ sum of <it>LGALS3 </it>and <it>BIRC5 </it>(AUC = 0.841, P < 0.0001). An application of multivariate logistic regression analysis resulted in the generation of a multiplex biomarker model based on <it>LGALS3, BIRC5, TFF3, CCND1, MET </it>and <it>CITED1 </it>that had considerably higher specificity than a single marker or two marker gene-based models (AUC = 0.895, P < 0.0001, 70.5% sensitivity and 93.4% specificity).</p> <p>Conclusions</p> <p>This study confirmed that mRNA expression levels of 7 out of 8 candidate genes analysed have a diagnostic value for the distinction of benign and malignant thyroid nodules. The multiplex biomarker model based on 6 genes outperformed a single marker or two marker-based models and warrants feasibility studies on FNA biopsies and the validation in a larger cohort of patients.</p>