Identification of DLAT as a potential therapeutic target via a novel cuproptosis-related gene signature for the prediction of liver cancer prognosis.

Abstract

The prognosis for liver cancer (LC) is dismal. Researchers recently discovered cuproptosis, a novel form of controlled cell death whose expression in LC and prognosis are unclear. This study reveals a gene signature to predict LC prognosis. RNA and clinical data for 371 LC patients were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were identified by comparing cancerous and normal samples. Genes linked to overall survival (OS) were found using univariate Cox regression and least absolute shrinkage and selection operator (LASSO). The gene signature was validated across all patients. Gene expression and clinical traits were analyzed, and Kaplan-Meier (KM) curves were generated for high- and low-risk groups. DEGs were used for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), immune infiltration, and drug prediction analyses. DLAT's functions were assessed using real-time polymerase chain reaction (RT-PCR), transwell invasion, Cell Counting Kit-8 (CCK-8), colony formation, and drug resistance assays. A total of 12 cuproptosis regulators were discovered in LC and normal liver tissues. A 3-gene signature based on LASSO Cox regression was utilized to categorize TCGA LC patients into low- and high-risk categories. Low-risk patients exhibited better survival than high-risk patients (P<0.05). Tumor grade, stage, and T stage differed between high- and low-risk groups. Long-term prognosis was well predicted by male subgroup survival studies. We predicted LC patient survival using sex, tumor grade, tumor stage, and risk score. Functional enrichment showed that extracellular matrix (ECM) architecture, channel function, and tumor-associated pathways were enriched in LC, suggesting that cancer related functions were collected. Immune microenvironment inhibition was found in the high-risk group suggesting that immunosuppression was closely related. We also discovered five small molecules that could be potentially useful for LC treatment. DLAT was discovered to promote the migration and proliferation of LC cells and is connected to drug resistance as a prognostic marker. Cuproptosis-related genes contribute to tumor development and can aid the prediction of LC patient prognosis. DLAT is a potential LC prognostic and therapeutic target.