ATP6AP1 drives pyroptosis-mediated immune evasion in hepatocellular carcinoma: a machine learning-guided therapeutic target

In our study, the machine learning-trained diagnostic model (AUC = 0.998) and the identified pyroptosis-related core gene ATP6AP1 provided an actionable strategy to overcome immune resistance in HCC. Mechanistically, ATP6AP1 stabilizes V-ATPase, which acidifies lysosomes, impairs antigen presentation, and drives pyroptotic inflammasome activation. This study highlights that ATP6AP1 plays a key role in promoting the lysosomal acidisis-pyroptosis-immunosuppression axis, and targeting ATP6AP1 can reshape the TME and enhance the efficacy of immunotherapy in HCC patients.