Lipid Metabolism–Related Genes Define Prognosis and Therapeutic Targets in Thyroid Cancer

Background Altered lipid metabolism is increasingly recognized as a driver of tumor progression, yet its specific role in thyroid cancer remains unclear. Methods We combined Mendelian randomization with transcriptomic and single‐cell analyses to identify lipid‐related factors that contribute to thyroid cancer development. A lipid‐metabolism gene signature was constructed to evaluate its prognostic value, and functional assays were used to examine the biological role of ACBD7. Results Lipid‐related metabolites showed genetic evidence of causal relevance to thyroid cancer. We identified a set of lipid‐metabolism genes that were consistently dysregulated in tumors and developed a nine‐gene signature that stratified patient prognosis with high accuracy. The high‐risk group displayed stronger lipid pathway activation, a distinct immune landscape, and a higher BRAF mutation rate. ACBD7 knockdown reduced thyroid cancer cell growth, invasion, and migration, suggesting a functional link between lipid metabolism and tumor aggressiveness. Conclusions Lipid metabolic dysregulation contributes to thyroid cancer progression and may help refine clinical risk assessment. The nine‐gene signature and the functional relevance of ACBD7 highlight the potential of lipid‐targeted strategies in future therapeutic development.