Related Experiment Video

Updated: Sep 1, 2025

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

6.8K

NOTCH4 mutation as predictive biomarker for immunotherapy benefits in NRAS wildtype melanoma

Hongxia Li1, Qin Zhang2,3,4, Qianqian Duan2,3,4

  • 1Department of Oncology, Shanxi Provincial People's Hospital, Taiyuan, China.

Frontiers in Immunology
|August 15, 2022
PubMed
Abstract

Insights

NOTCH4 mutations are linked to better outcomes in NRAS wildtype melanoma patients treated with immunotherapy. These mutations may enhance anti-tumor immunity and predict a stronger response to immune checkpoint inhibitors.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • NRAS wildtype melanoma represents approximately 80% of melanoma cases.
  • While NRAS wildtype melanoma generally shows better responses to immunotherapy than NRAS-mutant melanoma, the role of NOTCH family genes in this context is unclear.
  • NOTCH family genes are critical in both tumor cells and the tumor microenvironment (TME).

Purpose of the Study:

  • To investigate the association between NOTCH family gene variations and genomic factors influencing immune checkpoint inhibitor (ICI) response in NRAS wildtype melanoma.
  • To evaluate the correlation between NOTCH family gene mutations and clinical outcomes in NRAS wildtype melanoma patients undergoing ICI therapy.

Main Methods:

  • Genomic data from 265 NRAS wildtype, ICI-pre-treated melanoma samples across five cohorts were analyzed.
  • The study assessed the relationship between NOTCH family gene mutations and the efficacy of ICI therapy.

Main Results:

  • Melanomas with NOTCH4 mutations (NOTCH4-Mut) showed significantly prolonged overall survival (OS) in both discovery and validation cohorts.
  • NOTCH4-Mut melanoma exhibited superior clinical response rates (ORR) compared to NOTCH4 wildtype.
  • NOTCH4-Mut tumors displayed higher tumor mutation burden (TMB) and neoantigen burden (TNB), with increased mutations in the DNA damage response (DDR) pathway.
  • Gene set enrichment analysis indicated enhanced anti-tumor immunity in NOTCH4-Mut tumors.

Conclusions:

  • NOTCH4 mutations may enhance anti-tumor immunity in NRAS wildtype melanoma.
  • NOTCH4 mutation status could serve as a predictive biomarker for favorable immune responses to ICI therapy.
  • Identifying NOTCH4 mutations may help guide immunotherapeutic strategies in NRAS wildtype melanoma.
Keywords:
NRAS wildtypeanti-tumor immunitybiomarkerimmune checkpoint inhibitorsmelanoma

More Related Videos

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma08:18

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Published on: September 8, 2021

3.0K
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer07:59

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

1.2K

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...
4.4K
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...
2.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.4K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.8K