Bioinformatic Analysis of SERPINA1 Expression in Papillary Thyroid Carcinoma and Its Potential Association with Hashimoto's Thyroiditis

Abstract Purpose This study aims to explore the role of the SERPINA1 gene in papillary thyroid carcinoma (PTC) and its relationship with Hashimoto's thyroiditis (HT). Methods Transcriptomic data from The Cancer Genome Atlas (TCGA) were utilized to analyze differences in SERPINA1 expression between PTC patients with and without HT. The expression levels of SERPINA1 in tumor tissues and its association with tumor characteristics were assessed using the Wilcoxon test across both patient groups. The impact of SERPINA1 expression on immune cell infiltration in PTC was evaluated using the CIBERSORT tool. Single-cell transcriptomic data from the Gene Expression Omnibus (GEO) were further analyzed to identify SERPINA1-expressing subpopulations based on Thyroid Differentiation Score (TDS) and pseudotime analysis. Gene Set Variation Analysis (GSVA) was employed to characterize pathways associated with SERPINA1, inferring its potential functions. Finally, CellChat was used to investigate key ligand-receptor interactions between SERPINA1-positive subpopulations and other cell types. Results SERPINA1 expression was significantly elevated in PTC, particularly in cases with lymph node metastasis and extrathyroidal invasion. However, no significant effect of HT on SERPINA1 transcript levels was observed. SERPINA1 was primarily expressed in thyrocytes and myeloid cells, with differences in transcription levels and enriched SERPINA1-related GO pathways across their subpopulations. Some subpopulations expressed macrophage migration inhibitory factor (MIF), suggesting that SERPINA1 and MIF may have opposing regulatory effects on inflammation through glucocorticoid-related pathways. Conclusion SERPINA1 may promote PTC progression through multiple mechanisms, including complement system inhibition, involvement in epithelial-mesenchymal transition, modulation of lipid metabolism, and suppression of lymphocyte infiltration. In the context of HT, the effects of SERPINA1 on lipid metabolism in the tumor microenvironment may be more pronounced, which could potentially contribute to improved patient survival rates.