In-Depth Characterisation of miRNA and mRNA Transcriptome in Papillary Thyroid Carcinoma
By: Azliana binti Mohamad Yusof (azlianayusof@gmail.com)
The incidence rates of PTC has rapidly increased in the recent decades, and microRNA (miRNA) is one of the most studied biomarkers in this cancer. More than 50% of papillary thyroid carcinoma (PTC) patients presented with lymph node metastasis (LNM); the BRAF V600E mutation has been reported to be associated with this feature. This study aims to characterise the role of miRNA and mRNA involved in PTC pathogenesis and its relation with the BRAF V600E mutation. Next generation sequencing was performed to characterize miRNA and mRNA expression profiles in fresh frozen (FF) tumour-normal adjacent tissues of PTC LNM positive (PTC LNM-P) and PTC without LNM (PTC LNN). Bioinformatics integration and pathway analysis were performed to determine the regulatory networks involved. BRAF V600E status was determined in the discovery set with additional FFPE samples in a validation set. By setting the threshold at adjusted p value < 0.05 and log2 fold change ≤ -1.0 or ≥ 1.0, we observed that PTC LNM-P cases exhibited more dysregulated miRNAs than PTC LNN cases compared to their adjacent normal tissues. ECM-receptor interaction, cancer-associated proteoglycans and the MAPK pathway were among the significantly enriched pathways in PTC LNM-P. Four miRNAs that had significant expression ratios of 3p-to-5p in PTC LNM-P compared to PTC LNN were subjected to experiments in the validation phase. We found that expression of all miRNA were in concordance with miRNAseq data. In addition, through mRNAseq, PTC LNN cases exhibit more dysregulated genes compared to PTC LNM-P cases. BRAF V600E mutation was also found to be positively associated with LNM. MiRNA expression can be linked to the development of LNM of PTC. However, presence of LNM in PTC does not depend on the BRAF V600E mutation status. These findings may lead to better understanding of PTC pathogenesis.
