Related Experiment Video

Updated: Jan 12, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

7.2K

Notch pathway defines an aggressive and immune-suppressive phenotype associated with checkpoint inhibitor resistance

Yang Luo1, Roushu Wang2, Yu Xu3

  • 1Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Clinical and Experimental Medicine
|October 31, 2025
PubMed

Insights

High Notch pathway activation in gastrointestinal adenocarcinoma (GIAC) predicts poor prognosis and resistance to immune checkpoint inhibitors (ICIs). This suggests Notch inhibitors could enhance immunotherapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • The Notch pathway is crucial for gastrointestinal epithelium homeostasis and tumorigenesis.
  • Its role in cancer stem cells and immunity suggests a link to prognosis and treatment response in gastrointestinal adenocarcinoma (GIAC).

Purpose of the Study:

  • To investigate if Notch pathway activation predicts poor prognosis and resistance to immune checkpoint inhibitors (ICIs) in GIAC.
  • To develop a prognostic model based on Notch pathway gene expression.

Main Methods:

  • Analyzed Notch pathway mRNA expression and genomic alterations in TCGA datasets (ESAD, STAD, COAD, READ).
  • Constructed and validated a prognostic mRNA-score using TCGA and independent datasets.
  • Assessed associations with drug sensitivity, immune cell infiltration, and ICI efficacy in multiple cohorts.

Main Results:

  • Notch pathway genes showed conserved features across GIAC subtypes.
  • Higher Notch pathway expression correlated with shorter overall survival (OS), an immunosuppressive microenvironment, and poorer prognosis.
  • The validated mRNA-score predicted poor OS and ICI resistance in GIAC and other solid tumors.

Conclusions:

  • Notch pathway activation is a significant predictor of poor prognosis and ICI resistance in GIAC.
  • The developed mRNA-score algorithm can identify patients likely to benefit from or resist immunotherapy.
  • Targeting the Notch pathway may offer a strategy to overcome ICI resistance in cancer treatment.
Keywords:
Gastrointestinal adenocarcinomaICI resistanceNotch pathwayPrognostication

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.4K
Stimulation of Notch Signaling in Mouse Osteoclast Precursors08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

8.3K

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.4K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.2K