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Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Papillary thyroid carcinoma (PTC) is a common endocrine tumor with a rapidly increasing incidence. While surgery and radioactive iodine treatment are effective for most patients, they impose significant economic and psychological burdens. Metabolic dysregulation, particularly in fatty acid metabolism (FAM), plays a critical role in cancer progression and immune responses. Identifying key FAM-related genes in PTC may provide valuable biomarkers and potential treatment candidates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We analyzed 309 FAM-related genes to build a prognostic signature. DEGs were identified and a multivariate Cox regression model was utilized to establish a robust prognostic signature, which was validated by evaluating its associations with clinical features, immune responses, and tumor progression. Lastly, we examined the expression of key FAM-related genes in PTC cell lines and assessed that silencing <jats:italic>SCD<\/jats:italic> disturbs the proliferation, invasion, and migration of PTC cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three key FAM-related genes, <jats:italic>ACACB<\/jats:italic>, <jats:italic>ADH1B<\/jats:italic>, and <jats:italic>SCD<\/jats:italic>, as significant prognostic markers. Immunological analysis uncovered that low-risk patients exhibited higher immune cell abundance and increased expression of immune checkpoints, indicating a better response to immunotherapy. In contrast, high-risk patients showed lower immune cell abundance and immune checkpoint expression, suggesting poorer immunotherapy outcomes. Experimental validation demonstrated that <jats:italic>ACACB<\/jats:italic> and <jats:italic>ADH1B<\/jats:italic> were downregulated, while <jats:italic>SCD<\/jats:italic> was upregulated in PTC cell lines. Furthermore, silencing <jats:italic>SCD<\/jats:italic> inhibited PTC cell proliferation, migration, and invasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study underscores the pivotal role of FAM-related genes, particularly <jats:italic>ACACB<\/jats:italic>, <jats:italic>ADH1B<\/jats:italic>, and <jats:italic>SCD<\/jats:italic>, in the progression and immune regulation of PTC. The prognostic signature derived from these genes represents a valuable tool for predicting clinical outcomes and guiding personalized treatment strategies. Among these, <jats:italic>SCD<\/jats:italic> stands out as a promising therapeutic target for PTC, warranting further research to validate these findings and uncover its underlying molecular mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1534393","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T05:19:30Z","timestamp":1740633570000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Fatty acid metabolism influences the immune microenvironment in papillary thyroid cancer and identifies SCD as a novel 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