Comprehensive analysis of long noncoding RNA–mRNA co-expression patterns in thyroid cancer†

Abstract

Novel molecular-targeted treatments show great prospects for radioiodine-refractory and surgically inoperable thyroid carcinomas. While aberrations in protein-coding genes are a focus in molecular thyroid cancer medicine, the impact of oncogenes on the expression of long noncoding RNAs (lncRNAs) has been largely uncharacterized. We aimed to identify the expression patterns of lncRNAs and mRNAs in high-throughput molecular profiles of 18 papillary thyroid cancer (PTC) patients. We identified 452 mRNAs and 240 unannotated lncRNAs that were differentially expressed in PTC. Significantly enriched GO terms and pathways were identified, many of which were linked to cancer. By integrating the predicted lncRNA target genes with differentially expressed mRNAs, we identified 20 candidate lncRNAs in 45 PTC patients. Five lncRNAs (CTD-3193O13.11, RP5-1024C24.1, AC007255.8, HOXD-AS1, and RP11-402L6.1) were verified to be differentially expressed in PTC and to exhibit specific topological characteristics in the lncRNA–mRNA co-expression network. LncRNA CTD-3193O13.11 was determined to comprise a node of co-regulation with the other lncRNAs in PTC tumorigenesis. LncRNA RP5-1024C24.1, AC007255.8, and HOXD-AS1 expression was significantly related to clinical stage, lncRNA RP11-402L6.1 expression was associated with lymph node metastasis, lncRNA CTD-3193O13.11 expression was proportional to tumor size, and lncRNA AC007255.8 expression was proportional to patient age. Therefore, our study provides a genome-wide screening and analysis of lncRNA expression in PTC, which brings novel insights into the roles of lncRNAs in PTC progression.