Predicting prognosis,immune landscape,and drug targets with a novel signature for hepatocellular carcinoma

Abstract

Background

Despite advances in therapeutics, hepatocellular carcinoma (HCC) remains one of the most malignant types of digestive tract cancers with a poor prognosis. Pyroptosis is a form of programmed cell death induced by inflammatory caspases. Recent studies have identified pyroptosis, a form of programmed cell death induced by inflammatory caspases, as playing a role in tumorigenesis and cancer progression. However, the functions and mechanisms of pyroptosis in HCC are barely explored.

Methods

Gene expression and clinical data were derived from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A prognostic signature and nomogram were constructed by on differentially expressed genes and clinical data. Pathway enrichment and immune cell infiltration were further analyzed. Potential drugs to modulate the pathways were explored.

Results

In this study, a pyroptosis-related gene signature was developed and identified to be significantly correlated with the survival of HCC patients. Additionally, a nomogram on the basis of pyroptosis-related genes was constructed with distinct prognostic values. Furthermore, the pyroptosis-related gene signature might correlate with immune-related pathways and the regulation of the immune microenvironment, and several compounds (KIN001-220, TPCA-1, LY-303511, physostigmine, vemurafenib, etc.) could potentially reverse the pathogenic gene-expression patterns.

Conclusions: Our study provides evidence that pyroptosis is involved in HCC development, progression and immune microenvironment, which is promising in predicting the prognosis and developing targeted therapy.