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Human papillary thyroid carcinoma landscape and its immunological link with Hashimoto's thyroiditis at single cell resolution

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE163203 | GEO | 2021/07/01

REPOSITORIES: GEO

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Project description:PURPOSE: Amino acids (AAs) play important physiological roles in living cells. Some amino acid changes in blood are specific for autoimmune disorders, and some are specific for thyroid cancer. The aims of this study were to profile AA metabolites in the serum of patients with papillary thyroid carcinoma (PTC0) without Hashimoto’s thyroiditis (HT) and patients with PTC with HT (PTC1) and predict whether AA metabolites are associated with thyroid disease, thyroid hormone and thyroid autoantibodies. METHODS: A total of 93 serum samples were collected, including 28 healthy controls (HCs), 28 PTC0 patients and 37 PTC1 patients. Serum samples were analysed by high-performance liquid chromatography-triple stage quadrupole-mass spectrometry (HPLC-TSQ-MS), and 21 amino acids (AAs) were detected.RESULTS: The serum concentration of glutamic acid was significantly elevated in PTC1 patients compared with PTC0 patients. Lysine was the second amino acid that differentiated these two groups of PTC patients. In addition, the serum concentrations of glycine, alanine and tyrosine were significantly reduced in both PTC patient groups compared to the HC group. These AAs were also correlated with thyroid hormones and antibodies. Five amino acid markers, namely, glycine, tyrosine, glutamic acid, glutamine and arginine, separated/distinguished PTC0 patients from healthy subjects, and eight AA markers, the same AAs as above without arginine but with alanine, leucine, valine and histidine, separated/distinguished PTC1 patients from healthy subjects based on ROC analysis.CONCLUSION: Compared with the HCs, changes in AAs in PTC0 and PTC1 patients showed similar patterns, suggesting the possibility of a common pathophysiological basis, which confirms preliminary research that PTC is significantly associated with pathologically confirmed HT. We found two AAs, lysine and alanine, that can perform diagnostic functions in distinguishing PTC1 from PTC0.

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Human papillary thyroid carcinoma landscape and its immunological link with Hashimoto's thyroiditis at single cell resolution

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