Abstract
PDHA1 was associated with metabolic reprogramming in tumor progression. However, the clinical value of PDHA1, especially for prediction of drug sensitivity in hepatocellular carcinoma (HCC), has not been fully investigated. In this study, we found that PDHA1 expression was higher in HCC tissues compared to normal tissues and was correlated with poor prognosis in HCC patients. PDHA1 expression was mainly positively associated with immune cell infiltration using the TIMER, XCell, MCPCOUNTER, CIBERSORT, EPIC, and QUANTISEQ algorithms, which was validated by single-cell RNA-sequencing analysis. We also discovered that PDHA1 expression was correlated with six immune checkpoint-related genes. Univariate and multivariate Cox regression analyses revealed that PDHA1 expression was an independent prognostic indicator for HCC patients, and the nomogram incorporating PDHA1 expression exhibited excellent predictive capacity. Furthermore, PDHA1 expression was positively linked to the sensitivity of 5-fluorouracil, gemcitabine, paclitaxel, and sorafenib, and the molecular docking analysis demonstrated their excellent binding affinity.