Serum DLAT Is a Potential Diagnostic Marker in AFP-Negative HCC

The aim of this study was to analyze dihydrolipoyllysine-residue acetyltransferase (DLAT) expression and diagnostic ability in hepatocellular carcinoma (HCC), assess its role in HCC growth, and factors affecting it. We conducted bioinformatics analyses, examined DLAT expression and prognosis in pre-cancer, and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment studies while investigating its correlation with immunity. We also predicted regulatory factors, and detected DLAT in HCC cells using quantitative PCR (qPCR) and Western blotting, and in patient serum via enzyme-linked immunosorbent assay (ELISA). We found that DLAT was found to be upregulated in HCC and identified as an independent risk factor associated with immune cells. DLAT expression was regulated by hsa-miR-122-5p and the transcription factors zinc finger protein 148 (ZNF148), Myc-associated zinc-finger protein (MAZ), and Zinc finger and BTB domain-containing protein 12 (ZBTB12). Surprisingly, there was an increase in DLAT promoter methylation. The area under the receiver operating characteristic curves (AUCs) for serum DLAT in distinguishing HCC from healthy controls, high-risk individuals, and non-HCC cohorts were 0.905, 0.754, and 0.831, respectively. Combining DLAT with alpha-fetoprotein (AFP) improved diagnostic accuracy, with AUCs of 0.957, 0.819, 0.773, and 0.887 for the respective comparisons. Notably, serum DLAT was positive in 71.4% of AFP-negative HCC patients. And the transfection of hsa-miR-122-5p mimic could down regulate DLAT expression.