Genome-wide expression screening discloses long noncoding RNAs involved in thyroid carcinogenesis

Context: Long noncoding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood. Objective: To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics. Design:WeperformedRNAsequencing of 12 paired PTC tumorsandmatchednoncancerous tissues and correlated the expression of lncRNAs with clinical parameters. The 2 most significantly dysregulated lncRNAs were studied in an Ohio PTC cohort (n = 109) and in PTC data (n = 497) from The Cancer Genome Atlas. Setting: A combination of laboratory-based studies and computational analysis using clinical data and samples and a publically available database. Main Outcome Measures: Correlation between expression values and clinical parameters. Results: We identified 218 lncRNAs showing differential expression in PTC (fold change- 2.0, P = .01). Significant correlation was observed between the expression of 2 lncRNAs (XLOC-051122 and XLOC-006074) and 1) lymph node metastasis (N stage) and 2) BRAF(V600E) mutation. Among patients with wild-type BRAF, the expression of these 2 lncRNAs showed significantly higher levels in the patients with lymph node metastasis. In silico analysis of these lncRNAs pinpointed cell movement and cellular growth and proliferation as targeted functions. Conclusions: Comprehensive expression screening identified 2 novel lncRNAs associated with risk factors of adverse prognosis in PTC patients. These lncRNAs may be novel players in PTC carcinogenesis. (J Clin Endocrinol Metab 101: 4005-4013, 2016).