Analysis of Modular Hub Genes and Therapeutic Targets across Stages of Non-Small Cell Lung Cancer Transcriptome.

Autor:	Barretto AJB; School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila City 1002, Philippines.; School of Graduate Studies, Mapúa University, Manila City 1002, Philippines., Orda MA; School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila City 1002, Philippines.; School of Graduate Studies, Mapúa University, Manila City 1002, Philippines., Tsai PW; Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan., Tayo LL; School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila City 1002, Philippines.; School of Graduate Studies, Mapúa University, Manila City 1002, Philippines.; Department of Biology, School of Health Sciences, Mapúa University, Makati City 1203, Philippines.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2024 Sep 25; Vol. 15 (10). Date of Electronic Publication: 2024 Sep 25.
DOI:	10.3390/genes15101248
Abstrakt:	Non-small cell lung cancer (NSCLC), representing 85% of lung cancer cases, is characterized by its heterogeneity and progression through distinct stages. This study applied Weighted Gene Co-expression Network Analysis (WGCNA) to explore the molecular mechanisms of NSCLC and identify potential therapeutic targets. Gene expression data from the GEO database were analyzed across four NSCLC stages (NSCLC1, NSCLC2, NSCLC3, and NSCLC4), with the NSCLC2 dataset selected as the reference for module preservation analysis. WGCNA identified eight highly preserved modules-Cyan, Yellow, Red, Dark Turquoise, Turquoise, White, Purple, and Royal Blue-across datasets, which were enriched in key pathways such as "Cell cycle" and "Pathways in cancer", involving processes like cell division and inflammatory responses. Hub genes, including PLK1, CDK1, and EGFR, emerged as critical regulators of tumor proliferation and immune responses. Estrogen receptor ESR1 was also highlighted, correlating with improved survival outcomes, suggesting its potential as a prognostic marker. Signature-based drug repurposing analysis identified promising therapeutic candidates, including GW-5074, which inhibits RAF and disrupts the EGFR-RAS-RAF-MEK-ERK signaling cascade, and olomoucine, a CDK1 inhibitor. Additional candidates like pinocembrin, which reduces NSCLC cell invasion by modulating epithelial-mesenchymal transition, and citalopram, an SSRI with anti-carcinogenic properties, were also identified. These findings provide valuable insights into the molecular underpinnings of NSCLC and suggest new directions for therapeutic strategies through drug repurposing. Competing Interests: The authors declare no conflicts of interest.
Databáze:	MEDLINE
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