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Updated: Sep 14, 2025

Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
A Notch signaling pathway-related gene signature: Characterizing the immune microenvironment and predicting prognosis
Qingmiao Shi1, Shuwen Jiang1, Yifan Zeng1
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
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.
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