Prognostic Impact of the Lipid Metabolism Gene AGPAT4 in the Tumor Immune Microenvironment of Thyroid Cancer

Background Thyroid cancer (THCA), as a common endocrine malignancy, poses significant clinical challenges in terms of diagnosis and prognosis. This study aims to elucidate the role of AGPAT4, a gene involved in lipid metabolism, particularly fatty acid and glycerophospholipid metabolism, in thyroid cancer through bioinformatics analysis using data from The Cancer Genome Atlas (TCGA) database. Methods We analyzed the data of 512 thyroid cancer patients and 59 healthy individuals and constructed a protein-protein interaction (PPI) network involving AGPAT4 and its differentially expressed genes. The Kruskal-Wallis test and logistic regression were used to analyze the relationship between AGPAT4 expression and clinicopathological characteristics. Furthermore, Cox regression and Kaplan-Meier analysis were employed to evaluate its prognostic value. Moreover, single-sample gene set enrichment analysis (ssGSEA) revealed the association between AGPAT4 expression and the level of immune infiltration in the tumor microenvironment. Results AGPAT4 was expressed at low levels in thyroid cancer (P < 0.001) and could effectively distinguish tumor tissue from normal tissue (AUC = 0.942). Additionally, AGPAT4 expression was significantly correlated with pathological stage (P < 0.05). Kaplan-Meier survival analysis showed that patients with high AGPAT4 expression had better overall survival (HR = 0.28, P = 0.026). Cox regression analysis indicated that factors such as AGPAT4 expression, pathological stage (stage III/IV), and residual tumor (R1 and R2) were significantly associated with the prognosis of thyroid cancer patients. On the other hand, high AGPAT4 expression might be a prognostic protective factor, while advanced pathological stage and residual tumor indicated a risk of poor prognosis. The PPI network and functional enrichment analysis showed that AGPAT4 was involved in key pathways involved in the progression of thyroid cancer. Furthermore, immune infiltration analysis suggested an association between AGPAT4 expression and the immune response in the tumor microenvironment. Conclusion AGPAT4 may serve as a valuable biomarker for predicting the prognosis of thyroid cancer, providing insights into AGPAT4’s potential mechanisms and laying a foundation for future targeted therapies.