Identification Of Specific Long Non-Coding RNA Expression:Profile And Analysis Of Association With Clinicopathoiogical Characteristics And BRAF-mutation In Papillary Thyroid Cancer

Background:In recent years,long non-coding RNAs(lncRNAs)have been shown to play a critical regulatory role in cancer biology.However,the contribution of lncRNA to papillary thyroid cancer(PTC)remains largely unknown.Objective:In order to study the specific IncRNA profile and analysis the association with clinicopathological characteristics and BRAF-mutation in papillary thyroid cancerMethods:RNA sequencing and quantitative reverse transcription PCR(qRT-PCR)were used to detect and verify,respectively,changes to the transcriptomic profile in 12 PTC tissues compared to paired normal adjacent tissues.The potential functions of lncRNAs were predicted by examining annotations for the co-expressed mRNA and the statistical correlation between differentially expressed lncRNAs and clinicopathological characteristics was analysed.Furthermore,the specific subgroup patterns of the PTC transcriptome remodelled by BRAF mutations were also analysed.Results:A total of 188 lncRNAs and 505 mRNA were differentially expressed in 50%or more of the PTC tissues(fold change>2,p<0.05)as assessed by RNA-seq compared to paired normal adjacent tissues.Forty-seven lncRNAs and 39 mRNAs were verified in 31 pairs of PTC specimens using qRT-PCR,and the results were consistent with the RNA sequencing data.A co-expression network between differentially expressed lncRNAs and protein-coding RNAs was constructed and analysed,and functional analysis suggested that the differentially expressed genes mainly participate in ECM-receptor interactions and the focal adhesion pathway.The lncRNA NONHSAT076747 and NONHSAT122730 were associated with lymph node metastasis,and NONHSAT130622 expression was negatively correlated with tumour size.Furthermore,a specific PTC transcriptome subtype pattern stratified by BRAF mutation was also uncovered.The p53 signalling pathway was the most highly enriched pathway among the BRAF mutation-related genes.Conclusion:This study revealed specific changes to the IncRNA profile associated with PTC and provided new insight into its pathogenesis.The PTC-associated IncRNA NONHSAT130622,NONHSAT076747 and NONHSAT122730 might be potential diagnostic and therapeutic targets for PTC patients,and IncRNA with subtype-specific expression stratified by BRAF mutation might be significant in individual molecular subtypes.