ATG101-related signature predicts prognosis and therapeutic option in hepatocellular carcinoma

Autophagy plays a critical role in tumor pathogenesis. However, autophagy-related signature in Hepatocellular carcinoma (HCC) has not been revealed yet. We quantified the levels of various cancer hallmarks and identified ATG101 as the major risk factor for overall survival in HCC. A robust ATG101-related gene signature (ATS) for prognosis was constructed using a combination of bioinformatic and statistical approaches. Additionally, genetic and immunological properties were measured between ATS-high and ATS-low groups. The ATS signature was associated with shortened overall survival in HCC patients independently of clinicopathological characteristics. ATS status defines an inflamed yet exhausted tumor microenvironment, in which the activities of the exhausted CD8+ or CD4+ T cells were strongly associated with ATS. The ATS signature predicts the drug resistance to the immunotherapy, thus a combination of targeted therapy and immunotherapy might be suitable for ATS-high patients. This work shed light on the function of ATG101-related genes in HCC and revealed that the ATS signature may be a useful prognostic biomarker for differentiating molecular and immunological features and predicting probable response to the therapy.