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

We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous 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.