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Updated: Jul 4, 2025
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
A comprehensive integrated gene network construction to explore the essential role of Notch 1 in lung adenocarcinoma
1Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Abstract:
The heterogeneous biological landscape of non-small cell lung cancer (NSCLC) is largely attributed to the activation of Notch signalling pathway. Among the Notch family transmembrane proteins, neurogenic locus notch homolog protein1 (NOTCH1) is a putative oncogene in NSCLC which activates the pathway as negative prognostic factor. This study aims to explore integrated network approach in lung adenocarcinoma (LUAD) especially linked to the notch pathway and its receptors. Our gene set enrichment analysis reveals the key Notch pathway genes are predominantly down regulated in LUAD. There were 675 genes with a total of 6517 functional interactions and 6 densely connected clusters of 38 miRNAs, 84 transcription factors with 156 edges identified through network construction. Here we report five key genes namely NOTCH1, CDH1, ERBB2, GAPDH and COL1A1 significantly enriched in Notch pathway which are further validated through the KM plot, box plots, stage plots and TIMER analysis. In addition, the NOTCH1 receptor is strongly linked to the immune checkpoint inhibitor CD274 (PD-L1) and can be considered as prognostic marker and tumour suppressor gene in LUAD which surely provide the basis for early diagnosis and futuristic immunotherapeutic targets for LUAD.
Insights
Neurogenic locus notch homolog protein1 (NOTCH1) is a key factor in lung adenocarcinoma (LUAD). This study identifies NOTCH1 and related genes as potential prognostic markers and therapeutic targets for LUAD.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Non-small cell lung cancer (NSCLC) exhibits significant biological heterogeneity, often linked to Notch signaling pathway activation.
- Neurogenic locus notch homolog protein1 (NOTCH1) is implicated as a potential oncogene in NSCLC, negatively impacting prognosis.
- Lung adenocarcinoma (LUAD) biology, particularly its association with the Notch pathway, requires further investigation.
Purpose of the Study:
- To investigate the Notch signaling pathway and its associated genes in LUAD using an integrated network approach.
- To identify key genes within the Notch pathway that are dysregulated in LUAD.
- To explore the prognostic significance of identified genes and their relationship with immune markers in LUAD.
Main Methods:
- Gene set enrichment analysis to identify dysregulated Notch pathway genes in LUAD.
- Network construction to analyze functional interactions among genes, miRNAs, and transcription factors.
- Bioinformatic analyses including Kaplan-Meier plots, box plots, stage plots, and TIMER analysis for gene validation.
Main Results:
- Key Notch pathway genes were found to be predominantly downregulated in LUAD.
- Network analysis identified 6 densely connected clusters involving 38 miRNAs and 84 transcription factors.
- Five genes (NOTCH1, CDH1, ERBB2, GAPDH, COL1A1) were significantly enriched in the Notch pathway and validated as key players.
- NOTCH1 was strongly linked to CD274 (PD-L1), an immune checkpoint inhibitor.
Conclusions:
- NOTCH1, CDH1, ERBB2, GAPDH, and COL1A1 are significantly enriched in the Notch pathway and hold prognostic value in LUAD.
- NOTCH1 functions as a tumor suppressor gene and a prognostic marker in LUAD, associated with PD-L1 expression.
- These findings provide a basis for early diagnosis and suggest potential immunotherapeutic targets for LUAD.
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