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

<h4>Background</h4>Altered lipid metabolism is increasingly recognized as a driver of tumor progression, yet its specific role in thyroid cancer remains unclear.<h4>Methods</h4>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.<h4>Results</h4>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 <i>BRAF</i> mutation rate. ACBD7 knockdown reduced thyroid cancer cell growth, invasion, and migration, suggesting a functional link between lipid metabolism and tumor aggressiveness.<h4>Conclusions</h4>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.