Immunity plays an important role in tumor development. In this study, we aimed to investigate molecular classification and its prognostic value in hepatocellular carcinoma (HCC) based on immune signature. Gene set enrichment analysis (GSEA) was used to calculate scores of immune pathways for HCC and hierarchical clustering in two databases (The Cancer Genome Atlas [TCGA], Liver Cancer-RIKEN, JP [LIRI_JP]). The scores of the immune microenvironment and the proportions of 22 immune cells were also calculated. Single-sample GSEA (ssGSEA) was used to screen survival prognosis-related immune pathways and calculate the hazard radio of differentially expressed immune-related genes (IRGs), which were validated in clinical samples and multiple datasets. Based on the immune characteristics, we identified three HCC subtypes, namely immunity high (Immunity_H), immunity medium (Immunity_M), and immunity low (Immunity_L), and confirmed that the classification was reliable and predictable. Immunity_H with a higher immune and stromal score indicated better survival rate. Cox regression analysis showed that IL18RAP and IL7R were the protective genes. Immune risk score was the independent risk factor of overall survival in HCC patients. These results indicated that immunogenomic classification could distinguish HCC patients with different immune status, which could impact the prognosis of the patients with HCC.

Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on hepatocellular carcinoma (HCC) cells remain unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of integrative stress response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4–IGFBP1–Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.

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