Single-cell sequencing of tumor ecosystems in papillary thyroid carcinoma
Ontology highlight
ABSTRACT: The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profiled transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC.Our study illuminates a comprehensive landscape of PTC ecosystem that suggests potential prognostic and therapeutic implications. Our work not only adds dimensions to the biological underpinnings of PTC heterogeneity, but also provides a benchmark dataset for this malignancy.
Project description:Efficacy of a selective MEK (trametinib) and BRAFV600E (dabrafenib) inhibitors associated with radioactive iodine (RAI) for the treatment of refractory metastatic differentiated thyroid cancer with RAS or BRAFV600E mutation. To evaluate the objective response rate according to RECIST criteria in thyroid cancer patients with metastatic radioactive iodine (RAI) refractory disease, 6 months after a treatment combining in each arm of the phase II trial (patients with RAS mutation or patients with BRAFV600E mutation): - Arm A: 6 weeks of trametinib followed by RAI treatment (5.5 GBq following rhTSH) in patients with RAS mutation - Arm B: 6 weeks of trametinib plus dabrafenib followed by RAI treatment (5.5 GBq following rhTSH) in patients with BRAFV600E mutation
Project description:Efficacy of a selective MEK (trametinib) and BRAFV600E (dabrafenib) inhibitors associated with radioactive iodine (RAI) for the treatment of refractory metastatic differentiated thyroid cancer with RAS (current cohort) or BRAFV600E mutation. To evaluate the objective response rate according to RECIST criteria in thyroid cancer patients with metastatic radioactive iodine (RAI) refractory disease, 6 months after a treatment combining in each arm of the phase II trial (patients with RAS mutation or patients with BRAFV600E mutation): - Arm A: 6 weeks of trametinib followed by RAI treatment (5.5 GBq following rhTSH) in patients with RAS mutation - Arm B: 6 weeks of trametinib plus dabrafenib followed by RAI treatment (5.5 GBq following rhTSH) in patients with BRAFV600E mutation
Project description:About 20-30% of patients with metastatic non-medullary thyroid cancer (TC) have persistent or recurrent disease resulting from tumor dedifferentiation. Tumor redifferentiation to restore sensitivity to radioactive iodine therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activation for redifferentiation in thyroid cancer cell lines. Five, all digitalis-like compounds, restored hNIS expression and iodine uptake in TC cell lines. Upregulation of hNIS was mediated by intracellular Ca2+ and cFOS activation. Cell proliferation was inhibited by downregulating Akt1 and by induction of autophagy and p21-dependent cell cycle arrest. All together, digitalis-like compounds could represent a promising treatment modality for patients with dedifferentiated TC.
Project description:We performed gene and miRNA expression profiling in a series of 39 papillary thyroid carcinomas (PTCs) and 13 matched non-neoplastic thyroids derived from PTC patients with metastatic disease and submitted to radioiodine (RAI) treatment.
Project description:We performed gene and miRNA expression profiling in a series of 39 papillary thyroid carcinomas (PTCs) and 13 matched non-neoplastic thyroids derived from PTC patients with metastatic disease and submitted to radioiodine (RAI) treatment.
Project description:Papillary thyroid cancer (PTC) is a common endocrine tumor with rapidly increasing incidence in recent years. Although the majority of PTC are relatively indolen and have a good prognosis, it still has a certain proportion of PTC which is highly aggressive with lymphatic metastasis, iodine resistance and easy to recur. Circular RNAs as an class of noncoding RNAs are linked to a variety of tumor processes including PTC. In the current study, a circRNA deep sequencing was performed to identify alterations in circRNA expression levels of PTC tissues. CircTIAM1 was then selected as its increased expression in PTC and associated with migration, apoptosis and proliferation of PTC in vivo and in vitro. Mechanistically, circTIAM1 acted as a sponge of miR-646 and functioned in PTC through targeting mir-646 and HNRNPA1. Fluorescence in situ hybridization (FISH) and luciferase reporter assays further confirmed these connerctions. Overall, our results reveal an important oncogenic role of circTIAM1 in PTC and provide a potentially effective therapeutic strategy for PTC progression.
Project description:The tumor ecosystem heterogeneity of papillary thyroid carcinoma (PTC) is poorly characterized especially in children and young adult patients (CAYA-PTC). Here, we used single-cell RNA sequencing to profile transcriptomes map from eleven patients’ paratumors and localized tumors, covering comprehensive clinical courses of PTC. Compared with adult-PTC, CD4T_Tfh and CD8T_Tex cells were significantly higher in CAYA-PTC patients which closely related to metastasis. Along the differentiation trajectory, we discover three phenotypes of thyrocytes population (normal, BRAF-like, Fusion-like), whose composition shapes bulk molecular subtypes and tumor characteristics. Furthermore, our data identifies CAYA-PTC patients lack a “mild-state (BRAF-like)” malignant thyrocyte population. This different differentiation states indicates PTC cells quickly develop into invasion and metastasis in CAYA patients, while they gradually progress over a long time in adult patients. In addition, extracellular matrix cancer-associated fibroblasts(emCAFs_LAMP5) interact with endothelial cells and thyrocytes, ultimately promoting tumor angiogenesis and metastasis, which plays a more evident role in CAYA patients. FAP was highly expressed in emCAF_LAMP5 and positive correlated with LAMP5 in CAYA-PTC tissues. Therefore, ⁶⁸Ga-FAPI-PET have the potential to be used as a promising diagnostic method for CAYA patients with failed by traditional 18F-FDG-PET/CT. Together, our findings provide insight into the CAYA-PTC ecosystem that suggests distinct diagnostic, prognostic and therapeutic implications compared to adults.
2025-01-01 | GSE281736 | GEO
Project description:Gut microbiota for radioactive iodine therapy
Project description:Our main research focuses on the intervention of iodine-125 radioactive particles on liver cancer cells, inducing changes in gene expression, which may affect changes in biological characteristics. This provides clues for the potential mechanisms of iodine-125 radioactive particle therapy in liver cancer and offers new targets for disease treatment.
Project description:The dysregulation of circular RNAs (circRNAs) has been implicated in the development and progression of papillary thyroid cancer (PTC). In this study, we analyzed the dysregulated circRNA profile using PTC tissues and matched adjacent normal tissues by RNA-seq.