A PTEN-Autophagy Risk Model for the Prediction of Prognosis and Immune Microenvironment in Hepatocellular Carcinoma

The clinical behavior and molecular mechanisms of hepatocellular carcinoma (HCC) are complex and highly variable, limiting the discovery of new targets and therapies in clinical research. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is one of the tumor suppressor genes. It is of great interest to discover the role of unexplored correlation among PTEN, the tumor immune microenvironment, and autophagy-related signaling pathways and to construct a reliable risk model for prognosis during HCC progression.

We first performed differential expression analysis on the HCC samples. By using Cox regression and LASSO analysis, we determined the DEGs contributing to the survival benefit. In addition, the gene set enrichment analysis (GSEA) was performed to identify potential molecular signaling pathways regulated by the PTEN gene signature, autophagy, and autophagy-related pathways. ESTIMATE was also employed for evaluating the composition of immune cell populations.

We found a significant correlation between PTEN expression and the tumor immune microenvironment. The low-PTEN expression group had higher immune infiltration and lower expression of immune checkpoints. In addition, PTEN expression was found to be positively correlated with autophagy-related pathways. Then, differentially expressed genes between tumor and tumor-adjacent samples were screened, and 2895 genes were significantly associated with both PTEN and autophagy. Based on PTEN-related genes, we identified 5 key prognostic genes, including BFSP1, PPAT, EIF5B, ASF1A, and GNA14. The 5-gene PTEN-autophagy risk score (RS) model was demonstrated to have favorable performance in the prediction of prognosis.

In summary, our study showed the importance of the PTEN gene and its correlation with immunity and autophagy in HCC. The PTEN-autophagy.RS model we established could be used to predict the prognosis of HCC patients and showed significantly higher prognostic accuracy than the TIDE score in response to immunotherapy.