Abstract
The main types of thyroid neoplasms, follicular adenoma (FA), follicular thyroid carcinoma (FTC), classical and follicular variants of papillary carcinoma (clPTC and fvPTC), and anaplastic thyroid carcinoma (ATC), differ in prognosis, progression rate and metastatic behaviour. Specific patterns of lncRNAs involved in the development of clinical and morphological features can be presumed. LncRNA landscapes within distinct benign and malignant histological variants of thyroid neoplasms were not investigated. The aim of the study was to discover long noncoding RNA landscapes common and specific to major benign and malignant histological subtypes of thyroid neoplasms. LncRNA expression in FA, FTC, fvPTC, clPTC and ATC was analysed with comprehensive microarray and RNA-Seq datasets. Putative biological functions were evaluated via enrichment analysis of coexpressed coding genes. In the results, lncRNAs common and specific to FTC, clPTC, fvPTC, and ATC were identified. The discovered lncRNAs are putatively involved in L1CAM interactions, namely, pre-mRNA processing (lncRNAs specific to FTC); PCP/CE and WNT pathways (lncRNAs specific to fvPTC); extracellular matrix organization (lncRNAs specific to clPTC); and the cell cycle (lncRNAs specific to ATC). Known oncogenic and suppressor lncRNAs (RMST, CRNDE, SLC26A4-AS1, NR2F1-AS1, and LINC00511) were aberrantly expressed in thyroid carcinomas. These findings enhance the understanding of lncRNAs in the development of subtype-specific features in thyroid cancer.
Highlights
The main types of thyroid neoplasms, follicular adenoma (FA), follicular thyroid carcinoma (FTC), classical and follicular variants of papillary carcinoma, and anaplastic thyroid carcinoma (ATC), differ in prognosis, progression rate and metastatic behaviour
LncRNA expression was evaluated in the main histological subtypes of thyroid neoplasms, FA, FTC, fvPTC, clPTC, and ATC, compared to those in normal tissue (NT)
The number of genes analysed corresponded to the total number of long noncoding RNAs (lncRNAs) covered by uniquely mapped probes in the Affymetrix Human Genome U133 Plus 2.0 Array and the number of lncRNAs yielded after filtration by low number of counts for RNA-Seq datasets
Summary
The main types of thyroid neoplasms, follicular adenoma (FA), follicular thyroid carcinoma (FTC), classical and follicular variants of papillary carcinoma (clPTC and fvPTC), and anaplastic thyroid carcinoma (ATC), differ in prognosis, progression rate and metastatic behaviour. The aim of the study was to discover long noncoding RNA landscapes common and specific to major benign and malignant histological subtypes of thyroid neoplasms. LncRNAs common and specific to FTC, clPTC, fvPTC, and ATC were identified. Known oncogenic and suppressor lncRNAs (RMST, CRNDE, SLC26A4-AS1, NR2F1-AS1, and LINC00511) were aberrantly expressed in thyroid carcinomas These findings enhance the understanding of lncRNAs in the development of subtype-specific features in thyroid cancer. Based on the differences in mutational landscapes, morphology and clinical behaviour of histological subtypes, specific molecular patterns, including patterns of long noncoding RNAs (lncRNAs), are expected to be associated with these features. Investigation of lncRNAs common and specific to FA and FTC is important in understanding their relations and revealing differential diagnostic markers
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