A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas

Abstract

Background: Papillary thyroid cancer (PTC) incidence increased dramatically in children after the Chernobyl accident, providing a unique opportunity to investigate the molecular features of radiation-induced thyroid cancer. In contrast to the previous studies that included age-related confounding factors, we investigated mRNA expression in PTC and in the normal contralateral tissues of patients exposed and non-exposed to the Chernobyl fallout, using age- and ethnicity-matched non-irradiated cohorts.

Methods: Forty-five patients were analysed by full-genome mRNA microarrays. Twenty-two patients have been exposed to the Chernobyl fallout; 23 others were age-matched and resident in the same regions of Ukraine, but were born after 1 March 1987, that is, were not exposed to ¹³¹I.

Results: A gene expression signature of 793 probes corresponding to 403 genes that permitted differentiation between normal tissues from patients exposed and from those who were not exposed to radiation was identified. The differences were confirmed by quantitative RT-PCR. Many deregulated pathways in the exposed normal tissues are related to cell proliferation.

Conclusion: Our results suggest that a higher proliferation rate in normal thyroid could be related to radiation-induced cancer either as a predisposition or as a consequence of radiation. The signature allows the identification of radiation-induced thyroid cancers.

Figure 1

Global gene expression profiles of exposed and non-exposed normal and tumour tissues: PCA of the microarray data plotted with respect to first, second and third principal components. All probes were considered for the analysis. Tumour samples are shown in green (exposed) and in yellow (non-exposed), and normal samples are shown in red (exposed) and in blue (non-exposed). Abbreviation: Prin. Comp.=principal component.

Figure 2

Comparison of differential gene expression data obtained by microarrays and qRT-PCR on exposed and non-exposed normal tissues. The upper and lower limits of each box stand for the upper and the lower quartiles, respectively; bold lines represent medians; and whiskers represent the 10–90 percentiles. Regulation of serpine peptidase inhibitor clade E (SERPINE1), DUSP1, tribbles homologue 1 (TRIB1), calcium-binding protein A10 (S100A10), retinol dehydrogenase 12 (RDH12), annexin A1 (ANXA1) and guanine nucleotide-binding protein G(olf) subunit alpha (GNAL) was confirmed on 13 exposed normal contralateral tissues and 20 non-exposed normal contralateral tissues.