Multi-omics Insights\ninto PDHA1 as a Predictive Biomarker\nfor Prognosis, Immunotherapy Efficacy, and Drug Sensitivity in Hepatocellular\nCarcinoma

PDHA1 was associated with metabolic reprogramming in\ntumor progression.\nHowever, the clinical value of PDHA1, especially for prediction of\ndrug sensitivity in hepatocellular carcinoma (HCC), has not been fully\ninvestigated. In this study, we found that PDHA1 expression was higher\nin HCC tissues compared to normal tissues and was correlated with\npoor prognosis in HCC patients. PDHA1 expression was mainly positively\nassociated with immune cell infiltration using the TIMER, XCell, MCPCOUNTER,\nCIBERSORT, EPIC, and QUANTISEQ algorithms, which was validated by\nsingle-cell RNA-sequencing analysis. We also discovered that PDHA1\nexpression was correlated with six immune checkpoint-related genes.\nUnivariate and multivariate Cox regression analyses revealed that\nPDHA1 expression was an independent prognostic indicator for HCC patients,\nand the nomogram incorporating PDHA1 expression exhibited excellent\npredictive capacity. Furthermore, PDHA1 expression was positively\nlinked to the sensitivity of 5-fluorouracil, gemcitabine, paclitaxel,\nand sorafenib, and the molecular docking analysis demonstrated their\nexcellent binding affinity.