Project description: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:This research will evaluate the role of tissue proteome profile in regional metastatic disease. Considering that one of the main factors of survival in patients with papillary thyroid carcinoma is the presence of regional or distant metastatic disease, this research will focus on the difference in the proteome profiles between papillary thyroid carcinomas which had regional metastatic disease present at the time of surgery, and ones that did not have regional metastatic disease in neck lymph nodes at the time of surgery. In this study, 10 samples of papillary thyroid carcinomas without regional metastatic disease and 10 samples of well-differentiated papillary thyroid carcinomas with regional metastatic disease will be analyzed. The goal of this research is to try to identifiy certain differences in tissue proteomic profiles of papillary thyroid carcinoma depending on the presence of regional metastatic disease in neck lymph nodes.
Project description:Here we have performed quantitative and qualitative profiling of the proteome of cystic fluid from human cystic papillary thyroid carcinoma with the aim to identify specific proteins and pathways involved in cystic fluid from human cystic papillary carcinoma, as well as possible diagnostic markers.
Project description:Papillary thyroid carcinoma (PTC), the most common form of thyroid carcinomas, is a well-differentiated tumor and accounts for about 80% of all thyroid carcinomas. With the advantage of providing comprehensively analysis of global proteins in samples, proteomics techniques are increasingly applied in the field of identifying novel biomarkers in thyroid cancer. In this study, we conducted a TMT labeling-based quantitative proteomics analysis and bioinformatics analysis to compare the alternation of global proteins in tumor tissues and para-tumor tissues between PTC with LNM and without LNM.
Project description:RNA-Sequencing analysis of 18 papillary thyroid carcinoma biopsies and of 4 healthy donors' thyroids. In this analysis we assessed differential gene expression and investigated the mutational landscape in this tumor type. Analysis of gene fusion was also performed, leading to the identification of a novel chimeric transcript, potential driver in tumor initiation. Total RNA isolated from 18 papillary thyroid carcinoma biopsies and 4 healthy donors' thyroids.
Project description:Papillary thyroid carcinoma (PTC) is the most common malignant phenotype of thyroid cancer, with a rapidly increasing number of new cases globally. Multifocality is a common phenomenon in patients with PTC. The tumor microenvironment (TME) plays a pivotal role in cancer progression in papillary thyroid carcinoma (PTC), yet the composition and phenotype of cells within TME in bilateral PTCs are poorly understood.
Project description:Anaplastic thyroid carcinoma (ATC) has among the worst prognosis of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. BRAF and TP53 mutations co-occur in a high proportion of ATC, particularly those associated with a precursor papillary thyroid carcinoma (PTC). In order to develop an adult-onset model of BRAF-mutant anaplastic thyroid carcinoma, we generated a novel thyroid-specific CreER transgenic mouse. We utilize a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from papillary to anaplastic thyroid carcinoma. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis and rapid lethality. We employed small animal ultrasound imaging to monitor autochthonous tumors, and show that treatment with the selective BRAF inhibitor PLX4720 improved survival, but did not lead to tumor regression or suppress signaling through the MAPK pathway. Combination of PLX4720 and the MEK inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines, and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. Total RNA from five murine papillary thyroid carcinoma (PTC) tumors and five murine anaplastic thyroid carcinoma (ATC) tumors was analyzed.
Project description:Papillary thyroid carcinoma, as a malignant tumor with high incidence, is often accompanied by Hashimoto's thyroiditis. The pathogenesis of papillary thyroid carcinoma has not been fully clarified, and new molecular diagnostic methods are urgently needed to help the early and accurate diagnosis. In this study, the proteomic characteristics of papillary thyroid carcinoma in the context of Hashimoto's thyroiditis were analyzed by mass spectrometry, and the corresponding differential proteins and key pathways were screened to further study the pathogenesis and development mechanism.