Genomic analysis quantifies pyroptosis in the immune microenvironment of HBV-related hepatocellular carcinoma.

Abstract

Pyroptosis, a way of pro-inflammatory death, plays a significant part in the tumor microenvironment (TME). A recent study has shown that the hepatitis C virus changes the TME by inducing pyroptosis against hepatocellular carcinoma (HCC). However, compared to TME in hepatitis C virus-infected HCC, the exploration of immune characteristics and response to immunotherapy associated with the pyroptosis phenotype is still insufficient in hepatitis B virus-related HCC (HBV-HCC). Our study constructed pyroptosis-score (PYS) via principal-component analysis (PCA) to unveil the link between pyroptosis and tumor immunity in 369 HBV-HCC patients. Compared with the low-PYS group, subjects with higher PYS were associated with poor prognosis but were more susceptible to anti-PD-L1 treatment. In addition, we found that PYS can serve independently as a prognostic factor for HBV-HCC, making it possible for us to identify specific small molecule drugs with a potential value in inhibiting tumors via targeting pyroptosis. Also, the target genes predicted by the Weighted gene co-expression network analysis (WGCNA) and pharmacophore model were enriched in the HIF-1 signaling pathway and NF-kB transcription factor activity, which were related to the mechanism of inflammation-driven cancer. The PYS is extremely important in predicting prognosis and responses to immunotherapy. New treatment strategies for inflammation-driven cancers may be found by targeting pyroptosis.