Identifying DLAT as a novel therapy target based on integration analysis of the cuproptosis regulatory genes for hepatocellular carcinoma

Cuproptosis is a newly found Regulated Cell Death (RCD) form, dependent on copper and mitochondrial respiration. However, limited available researches of the roles of cuproptosis regulators in prognosis and development of Hepatocellular Carcinoma (HCC) prompted us to conduct this investigation. In our study, we systematically analyzed the expression levels and prognostic profiles of 27 cuproptosis regulatory genes in HCC samples downloaded from The Cancer Genome Atlas (TCGA) cohort and developed a prognostic risk model based on 7 genes (NDUFA1, NDUFB2,DLD, DLAT, MTF1, ATP7B, GCSH) by performing step AIC method and multivariate cox regression analysis. The independent prognostic values of the risk score were also validated in the external International Cancer Genome Consortium (ICGC) cohort. Moreover, the Overall Survival (OS) of HCC patients in the low-risk group was significantly longer than that in the high-risk group. Notably, the expression level of DLAT was found to be higher in the HCC tissues compared with normal tissues and high DLAT expression correlated with a poor prognosis. The function of DLAT was further validated in vitro using siRNA tool, DLAT depletion inhibited the proliferation and migration of HCC cells which indicated that DLAT was a potential and promising therapeutic target for HCC.