A novel lactylation-related signature predicts the prognosis and is associated with immune infiltration in thyroid cancer

Background​: Epigenetic regulator lactate, a glycolysis product, affects gene expression via histone lactylation, promoting tumor growth and immunosuppression. But its related genes' role in thyroid carcinoma (THCA) remains unclear.​ Methods​: Lactylation - related genes from TCGA were consensus clustered. DEGs between clusters were analyzed via Cox regression, Random_forest, and LASSO to create a Lactylation - related High/Low risk signature. TCGA data was split for validation. Immune cell infiltration, GSEA, TIDE score and drug sensitivity of the subtypes were examined. A lactylation scoring model was built as per prior method, and lactate levels of "Two risk" and "Two cluster" were compared. Signature gene expression was detected in TCGA - THCA and GSE33630 datasets. Results​: Ten lactylation - related DEGs formed 2 prognostic - valuable (p = 0.01) consensus clusters for THCA. 137 prognostic DEGs were identified in these clusters. A 7 - gene lactylation - related signature (High risk and Low risk) showed a significant survival correlation (p < 0.001). Immune cell infiltration and GSEA analysis showed higher immune cell infiltration and activity in the low - risk group. The Exclusion score suggested immune escape in the high - risk group. A nomogram including risk score was established for survival prediction. A lactylation scoring model showed Cluster B and the High - risk group had higher lactylation levels and poor prognoses. High lactylation was linked to a high Exclusion score, indicating more immune escape. Validation in TCGA and GSE33630 THCA samples showed high CLDN2, ARSI, SPOCD1, TUBB3 and low ATP2C2 expression. In conclusions ​, the lactylation signature can not only serve as a prognostic marker for thyroid carcinoma (THCA), but may also provide new therapeutic targets for it. Future studies should further validate the potential of this signature for clinical application.