The discovery and validation of genes associated with lactylation in papillary thyroid cancer

Thyroid cancer is the most common endocrine malignancy. Lactic acid and acidification of the tumor immune microenvironment are key processes promoting carcinogenesis. This study was to identify genes related to lactylation in papillary thyroid cancer (P​TC) and explore potential regulatory mechanisms. Lactylation-associated genes were identified by combining differential expression and regression analyses, and these genes were subsequently used to construct a risk model. Functional enrichment analysis, immune microenvironment profiling, and drug sensitivity assessment were then performed. In addition, lactylation-associated genes scores were evaluated at the single-cell level, and key cell populations were identified. Finally, the expression of lactylation-associated genes was assessed in clinical samples. After multiple rounds of selecting, MTTP, FOSB, and JUN were identified as candidate lactylation-associated genes. A risk model was then constructed to classify PTC patients into a high risk group (HRG) and a low risk group (LRG), with HRG patients showing poorer prognosis. The “primary immunodeficiency” signaling pathway was associated with HRG and LRG. Significant differences were observed in the infiltration levels of endothelial cells and neutrophils between the HRG and LRG. Erlotinib_1168 were predicted to be more sensitive in the LRG, whereas Camptothecin_1003 and Vinblastine_1004 were predicted to be more sensitive in the HRG. Finally, single-cell analysis identified six cell types, among which T/natural killer cells, myeloid cells, B cells, thyrocytes, and myeloid cells were prioritized as candidate key cells by AUCell scoring of lactate-related gene set and the three-gene prognostic signature for subsequent pseudotime analysis. Experimental results show that, compared to the control group, MTTP, FOSB, and JUN were downregulated in tumors. MTTP, FOSB, and JUN were identified as lactylation-associated genes in PTC, offering preliminary clues for further investigation of targeted therapies.