Bioinformatic analysis of serpina1 expression in papillary thyroid carcinoma and its potential association with Hashimoto's thyroiditis.

Abstract

Purpose: Previous studies have suggested that SERPINA1 may promote a better prognosis in papillary thyroid carcinoma (PTC) along with Hashimoto's thyroiditis (HT). This study aims to further explore the role of the SERPINA1 gene in PTC and its relationship with HT using multiple databases.

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: TCGA data analysis reveals that, compared to normal thyroid tissue, the transcriptional level of SERPINA1 is significantly elevated in PTC tissues. Moreover, the expression of SERPINA1 is closely linked to certain clinical pathological features of PTC and the infiltration of immune cells in the tumor microenvironment. Single-cell transcriptome analysis reveals that SERPINA1 is primarily expressed in thyrocytes and myeloid cells. In thyrocytes, SERPINA1 is associated with complement-related proteins (e.g., C3, CD55). In poorly differentiated thyrocytes, it is linked to protease inhibitors and epithelial-mesenchymal transition (EMT) pathways, while in moderately differentiated thyrocytes, it associates with apolipoproteins APOE and APOC1. In macrophages, SERPINA1 is highly expressed in HT-associated macrophages and unpolarized macrophages, correlating with inflammation and extracellular matrix regulation pathways. Cell-cell interaction analysis indicates that SERPINA1-positive cells interact with other cells in the tumor microenvironment through macrophage migration inhibitory factor (MIF) and fibronectin 1 (FN1).

Conclusion: Compared to normal thyroid tissue or cells, the expression level of SERPINA1 is elevated in PTC. In cancer cells, SERPINA1 may be associated with the complement system and complement regulator functions. In poorly differentiated thyrocytes, SERPINA1 may primarily function as a protease inhibitor and is closely related to FN1. In moderately differentiated thyrocytes, SERPINA1 is associated with apolipoproteins. In unpolarized macrophages, the function of SERPINA1 may be to act as a serine protease inhibitor, participating in the remodeling of the extracellular matrix. In macrophages within an HT environment, the elevated expression of SERPINA1 may serve as a protective mechanism to limit inflammation. In the tumor microenvironment coexisting with HT, SERPINA1 outside the tumor cells may enter the tumor cells through lipid metabolism pathways. The potential role of SERPINA1 in PTC progression is complex, and the findings of this study require further validation.