Molecular pathways associated with mortality in papillary thyroid cancer

BackgroundA better understanding of the molecular mechanisms involved in papillary thyroid cancer (PTC)-associated adverse outcome is needed to manage these patients effectively. Our objectives were to identify molecular pathways associated with unfavorable features and outcomes in patients with PTC.MethodsWe performed genome-wide expression (GWE) analysis in 64 human tissue samples affected by PTC. Clinical, pathologic, and microarray data were analyzed to identify differentially expressed genes and pathways associated with unfavorable outcomes. Gene set enrichment analysis (GSEA) was used to determine which molecular pathways are associated with mortality.ResultsGWE analysis identified 43, 115, and 40 genes that were significantly differentially expressed by gender, tumor differentiation status, and mortality, respectively, with a false-discovery rate of <5%. For mortality, GSEA revealed 7 enriched pathways, including transfer RNA synthesis, mitochondria and oxidative phosphorylation, porphyrin and chlorophyll metabolism, and fatty acid synthesis. Leading-edge analysis showed that 341 genes were significantly involved in the enriched pathways. Cluster analysis using 100 differentially expressed genes showed complete separation of patients by mortality.ConclusionTo our knowledge, this is the first GWE analysis of PTC and adverse outcomes. We found 11 molecular pathways that were significantly associated with mortality resulting from PTC. A 100-gene signature completely separates patients with and without PTC-associated mortality.