A Notch signaling pathway-related gene signature: Characterizing the immune microenvironment and predicting prognosis in hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES

Prior studies have highlighted an escalating global burden of hepatocellular carcinoma (HCC). The Notch signaling pathway regulates the initiation and development of HCC and determines the HCC prognosis.

METHODS

The expression data of genes related to the Notch signaling pathway were acquired from public databases. To filter prognostic gene signatures and establish the risk model, the analyses of consensus clustering, least absolute shrinkage and selection operator (LASSO), and multivariate Cox were conducted. Subsequently, the risk stratification was optimized using a decision tree and nomogram. The immune landscapes were revealed utilizing the single-sample gene set enrichment analysis, and tumor immune dysfunction and exclusion score.

RESULTS

According to the mRNA expression profile of Notch signaling pathway-related genes, HCC patients were stratified to three clusters, which have different survival probability and immune infiltration characteristic. Subsequently, we developed a risk model based on five prognostic Notch signaling-related gene signatures (SPP1, SMG5, HMMR, PLOD2, and CFHR4). The model demonstrated an accurate estimation of overall survival, revealing alterations in immune status and immunotherapy sensitivity among HCC patients with different risk scores.

CONCLUSIONS

This study constructed a Notch signaling pathway-related prognostic model, offering valuable insights for the assessment of immune characteristics and immunotherapy responses in HCC patients.