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Introduction: PTC is not generally considered a lethal disease, but prone to recurrence as the prognosis. Hashimoto's thyroiditis (HT) is an important factor that affects the prognosis of papillary thyroid carcinoma (PTC). It is crucial to find biomarkers to identify the combination of HT with PTC and to predict the prognosis. Methods: RNASeq data from the Cancer Genome Atlas (TCGA) database was used to screen differentially expressed genes (DEGs) of PTC with HT via the edgeR package of R software version 3.3.0. Also, the DEGs were applied to the DAVID web-based tool to determine the enrichment of gene functions via Gene Ontology (GO) analysis and to identify associated pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. By constructing protein interaction networks within Cytoscape software, we screened candidate genes and explored possible relationships with the clinical phenotype of PTC. Finally, additional thyroid tissue samples were collected to verify the results above. Results: After analyzing the RNA-Seq data of PTC patients from the Cancer Genomic Atlas, 497 differentially expressed PTC genes were found to be associated with HT, of which protein tyrosine phosphatase receptor type C (PTPRC), KIT, and COL1A1 were associated with tumor size and lymph node metastasis (p < 0.05). Verification of these results with another 30 thyroid tissues of clinical PTC patients revealed that the expression level of PTPRC in the PTC with HT group was higher than that in the PTC without HT group (p < 0.05) and the ROC curve showed a good discrimination (area under the curve = 0.846). However, the correlation with the clinical phenotype was not statistically significant (p > 0.05). Discussion: These data suggest that upregulation of PTPRC enhances the incidence of HT associated with PTC and is also predictive of a poor prognosis. [ABSTRACT FROM AUTHOR]

• Anti-PD-1-associated thyroid immune damage is associated with women, IgG4 subtypes of drugs, the baseline and changes in thyroid function, antibodies, and hormone sensitivity. • Head and neck cancers have the highest risk of thyroid irAE, which may be associated with squamous carcinoma. • Those with abundant peripheral blood lymphocytes before treatment are susceptible to irAE hypothyroidism; those with significant lymphocytosis before and after treatment are susceptible to irAE hyperthyroidism and thyroiditis. • Anti-PD-1 increases the immunosensitivity of thyroid cells by downregulating AKT1-SKP2 and inducing thyroid irAE. Immune checkpoint inhibitors evoke the immune system, which may cause immune-related adverse effects. The predictors and mechanisms of anti-PD-1-associated thyroid immune injury remain unclear. A retrospective analysis is conducted on 518 patients treated with anti PD-1/PD-L1. Firstly, the differences between anti PD-1 and anti PD-L1 are compared on the risk of thyroid immune injury. Then, the predictors of the risk and thyroid function for anti PD-1 related thyroid immune injury are analyzed. Furthermore, the in vitro mechanism of normal thyroid cells (NTHY) is studied. First, the effect of anti PD-1 on the cell viability and immune sensitivity of thyroid cells is observed. Cell viability includes cell proliferation, apoptosis, cell cycle, T4 secretion, while immune sensitivity includes molecular expression and CD8 + T cell aggregation and killing towards NTHY. Then the differentially expressed proteins (DEPs) are screened by protein mass spectrometry. Enrichment of KEGG pathway and annotation of GO function on DEPs are conducted. Human protein–protein interactions are obtained from STRING database. The network is constructed and analyzed using Cytoscape software. In vitro, key proteins and their pathways are validated through overexpression plasmids or inhibitors. The recovery experiment and the immuno-coprecipitation experiment are designed to support the results. In vivo, the key proteins are detected in the thyroid tissue of mice fed with anti PD-1, as well as in the thyroid tissue of patients with Hashimoto's thyroiditis. Thyroid irAE is associated with female, IgG, FT4, TPOAb, TGAb, TSHI, TFQI, and TSH. Peripheral lymphocytes are associated with thyroid function. In vitro, the NIVO group shows prologed G1 phase, decreased FT4, downregulated PD-L1, upregulated IFN-γ, and more CD8 + T cell infiltration and cytotoxicity. AKT1-SKP2 is chosen as the key protein. AKT1 overexpression and SKP2 inhibitor replies to NIVO and AKT1 overexpression, respectively. Immunoprecipitation shows SKP2 and PD-L1 interaction. Female, impaired thyroid hormone sensitivity and IgG4 contribute to the risk of thyroid irAE, while peripheral blood lymphocyte characteristics affect thyroid function. Anti-PD-1 induces thyroid irAE by downregulating AKT1-SKP2 to enhance thyroid immunosensitivity. [ABSTRACT FROM AUTHOR]