Clinical and experimental medicine 2016 12 2117(4) 555-564 doi 10.1007/s10238-016-0445-y
Although papillary thyroid cancer is a relatively indolent malignancy, its progression may be associated with dedifferentiation and resistance to radioactive iodine treatment. In this study, patterns of differentially expressed genes in association with disease progression were systemically evaluated. We firstly performed transcriptome analyses for four matched cancerous and noncancerous tissue pairs of the classical subtype of papillary thyroid cancer. Among the upregulated and downregulated genes, the expression of 164 and 183 genes increased and decreased, respectively, from stage I to stage IV. Functional enrichment and pathway analysis showed that angiogenesis pathway was upregulated, whereas oxidation-reduction and metabolism of reactive oxygen species were downregulated. Teneurin transmembrane protein 1 (TENM1) expression was highly upregulated in cancerous tissues and negative in benign thyroid tissues. By immunohistochemistry, TENM1 expression in papillary thyroid cancer was associated with the classical subtype (p = 0.018), extrathyroidal invasion (p = 0.001), BRAF V600E mutation (p < 0.001), and an advanced stage (p = 0.019). Taken together, our results indicate that distinct pathways are involved in papillary thyroid cancer progression, and TENM1 is a potential marker of cancer progression.