Abstract
BACKGROUND: Thyroid cancer (THCA) is a common malignant tumor of the endocrine system, and significant clinical challenges remain in its diagnosis and prognostic evaluation. This study aims to elucidate the role of AGPAT4 in thyroid cancer by investigating its expression, involvement in metabolic pathways, and potential as a prognostic biomarker. METHODS: We analyzed data from 512 thyroid cancer patients and 279 controls, performed differential expression analysis of AGPAT4 in thyroid cancer, analyzed the gene expression correlation of AGPAT4 in thyroid cancer, and the protein-protein interaction (PPI) network and functional enrichment analysis of AGPAT4 and its differentially expressed genes (DEGs) were constructed. The Kruskal-Wallis test and receiver operating characteristic (ROC) curve analysis were used to investigate the correlation between AGPAT4 expression and clinicopathological characteristics as well as its diagnostic efficacy. Cox regression analysis and Kaplan-Meier analysis were employed to evaluate its prognostic value. Additionally, single-sample gene set enrichment analysis (ssGSEA) was utilized to explore the association between AGPAT4 expression and the level of immune infiltration in the tumor microenvironment. RESULTS: Our findings revealed that AGPAT4 was significantly downregulated in thyroid cancer (THCA) tissues (P < 0.001), suggesting a potential tumor-suppressive role of AGPAT4 in thyroid cancer. AGPAT4 exhibited robust efficacy in distinguishing tumor tissues from normal tissues, with an area under the receiver operating characteristic curve (AUC) of 0.973. Furthermore, AGPAT4 expression levels were significantly correlated with pathological stage and survival rate (P < 0.05). Kaplan-Meier survival analysis showed that patients with high AGPAT4 expression had better progression-free interval (PFI) (HR = 0.45, P = 0.007). Protein-protein interaction (PPI) network and functional enrichment analyses revealed that AGPAT4 is involved in key pathways associated with thyroid cancer progression. Immune infiltration analysis suggested an association between AGPAT4 expression and immune responses in the tumor microenvironment. CONCLUSION: AGPAT4 holds promise as a potential biomarker for the differential diagnosis and prognostic assessment of thyroid cancer, thereby providing a possible reference for the further exploration of therapeutic strategies against this disease.