MiRNA Expression Pattern in Papillary Thyroid Cancer
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ABSTRACT:
PROVIDER: PRJNA789823 | ENA |
REPOSITORIES: ENA
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Project description:The aim of this study was to conduct a comparison of tissue miRNA in thyroid cancer (papillary (PTC), follicular (FTC), and microcancer (PTMC)) and healthy thyroid tissue (Control). The expression level of 798 miRNAs using NanoString technology was examined. ROC curve analysis, and logistic regression modeling were performed. Gene ontology (GO), canonical pathways analysis were used to explore the biological functions of the miRNA target genes. The study revealed that 10 miRNAs were deregulated in samples of patients with PTC. Pathway analysis showed that miRNA target genes were mainly significantly enriched in endocrine resistance, EGFR tyrosine kinase inhibitor resistance, and pathways in cancer. ROC analysis demonstrated that miR-146-5p, miR-551b-3p, and miR-222-3p can be introduced as a diagnostic tool for PTC (AUC=0.770; 0.740; 0.720; respectively). Validation by qRT-PCR confirmed our findings. The results suggest that tissue miRNAs can potentially be used as predictive biomarkers of PTC in patients.
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Project description:Tumor microenvironment heterogeneity sheltered our understanding of papillary thyroid cancer. However, molecular characteristics of papillary thyroid cancer has not been reported at single cell resolution. The immunological link between papillary thyroid cancer and Hashimoto's thyroiditis is also in doubt.We identified 24 cell clusters in human papillary thyroid cancer based on their heterogeneous gene expression pattern. Follicular epithelial cell subsets in papillary thyroid cancer with Hashimoto's thyroiditis and papillary thyroid cancer without Hashimoto's thyroiditis showed different malignant level. Machine learning model identified potential biomarker to evaluate tumor epithelial cell development. Together with immunostaining, lymphocytes heterogeneity indicated an obvious B cell infiltration pattern in papillary thyroid cancer with Hashimoto's thyroiditis. Additionally, trajectory analysis of B cell and plasma cell suggest the migration potential from normal adjacent tissue of Hashimoto's thyroiditis to papillary thyroid cancer tissue. Our results provide the first single cell landscape of Papillary thyroid cancer. Single cell data resource of Papillary thyroid cancer with Hashimoto's thyroiditis promote our understanding of molecular heterogeneity and immunological link between papillary thyroid cancer and Hashimoto's thyroiditis.
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Project description:3 papillary thyroid cancer cell lines were compared, treated with Y15 to untreated. 1 million cells of each papillary thyroid cell line (TPC1, K1, BCPAP) were plated, treated 24 hours later with 10uM Y15, and collected 24 hours later by trypsinization.
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Project description:Mice with thyroid-specific expression of oncogenic BRAF (Tg-Braf) develop papillary thyroid cancers (PTC) that are locally invasive and have well-defined foci of poorly differentiated thyroid carcinoma (PDTC). To investigate the PTC-PDTC progression, we performed a microarray analysis using RNA from paired samples of PDTC and PTC collected from the same animals by laser capture microdissection. Analysis of 8 paired samples revealed a profound deregulation of genes involved in cell adhesion and intracellular junctions, with changes consistent with an epithelial-mesenchymal transition (EMT). This was confirmed by IHC, as vimentin expression was increased and E-cadherin lost in PDTC compared to adjacent PTC. Moreover, PDTC stained positively for phospho-Smad2, suggesting a role for transforming growth factor-beta (TGFbeta) in mediating this process. Accordingly, TGFbeta induced EMT in primary cultures of thyroid cells from Tg-Braf mice, whereas wild-type thyroid cells retained their epithelial features. TGFbeta-induced Smad2 phosphorylation, transcriptional activity and induction of EMT required MAPK pathway activation in Tg-Braf thyrocytes. Hence, tumor initiation by oncogenic BRAF renders thyroid cells susceptible to TGFbeta-induced EMT, through a MAPK-dependent process. Comparing the transcription profiles of 8 pairs of murine poorly differentiated thyroid cancer and papillary thyroid cancer collected from the same animals by laser capture microdissection. Co-hybridizations were done in triplicate with a single dye flip.
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