A Notch signaling pathway-related gene signature: Characterizing the immune microenvironment and predicting prognosis in hepatocellular carcinoma
Qingmiao Shi, Shuwen Jiang, Yifan Zeng, Xin Yuan, Yaqi Zhang, Qingfei Chu, Xue Chen, Lanjuan Li
Abstract
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.