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Research Article

A comprehensive integrated gene network construction to explore the essential role of Notch 1 in lung adenocarcinoma (LUAD)

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Received 16 Aug 2023, Accepted 10 Jan 2024, Published online: 28 Jan 2024
 

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.

Communicated by Ramaswamy H. Sarma

Acknowledgements

The authors would like to acknowledge the Vellore Institute of Technology, Vellore, for providing the facilities and encouragement to carry out this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Pearl John: Drafting of paper, analysis and interpretation of data and visualisation.

C. Sudandiradoss: Conception and design, revising it critically for intellectual content and final approval of version to be published.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

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