Decreased expression of 3-hydroxybutyrate dehydrogenase 1 is a prognostic marker and promotes tumor progression in hepatocellular carcinoma

Growing evidence indicates that altered metabolism represents the hallmark of hepatocellular carcinoma (HCC). The mitochondrial 3-hydroxybutyrate dehydrogenase 1 (BDH1) is a key catalytic enzyme in ketogenesis with unknown roles in HCC. Hundred and four tissue sample pairs (HCC tissues, n = 104; matched normal tissues, n = 104) were obtained and analyzed with immunohistochemical (IHC) staining to investigate the clinical and functional role and the diagnostic and prognostic value of BDH1 in HCC. In addition, RNA-Seq datasets from the Tumor Immune Estimation Resource (TIMER) (HCC group, n = 371; normal group, n = 50) and microarray datasets from the Gene Expression Omnibus (GEO) database (HCC tissues, n = 1671; normal tissues, n = 1479) were used to assess BDH1 expression in HCC. Several bioinformatic methods were performed to identify pathways regulated by BDH1. The IHC staining showed that BDH1 expression decreased in HCC tissues (n = 69) compared with that in adjacent normal tissues (n = 35, P < 0.001). Low BDH1 expression was associated with advanced clinical stage (P = 0.033) and vascular invasion (P = 0.007). Moreover, ectopic expression of BDH1 reduced tumor proliferation and suppressed the migration and invasion of HCC cells in vitro. Therefore, our data suggest that BDH1 is a potentially valuable diagnostic biomarker and therapeutic target for HCC.