Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Lipid metabolism is essential for cancer development. Nicotinamide nucleotide transhydrogenase (NNT) is abnormally expressed in multiple cancers; however, its role in HCC is unclear. We assessed the NNT expression level in The Cancer Genome Atlas (TCGA) cohort and Gene Expression Omnibus (GEO) datasets and found that the expression level of NNT was lower in HCC patients than non-cancer control subjects in the public databases. Survival analysis was conducted according to high and low NNT expression. Low NNT expression was significantly associated with a poor prognosis. For confirmation, the gene and protein expression of NNT in cancer and adjacent non-cancer tissues from HCC patients at our institute cohort indicated the lower expression level of NNT in cancer compared to adjacent non-cancer tissues using quantitative polymerase chain reaction and western blot, respectively. Bioinformatics was used to analyze the underlying mechanisms and establish the protein-protein interaction network of NNT. It showed that NNT is associated with functions of bile acid and fatty acid metabolism and their related genes. To conclude, our results supported that NNT expression is downregulated in HCC, and can serve as a novel prognostic biomarker.
Keywords: Hepatocellular carcinoma; lipid metabolism; nicotinamide nucleotide transhydrogenase; prognosis.
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