Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients

Lung squamous cell carcinoma (LUSC) is a deadly cancer, characterized by its complex genetic profiles. Additionally, the molecular mechanisms and etiology underlying LUSC growth are less extensively characterized as compared to adenocarcinoma subtype of lung cancer. Therefore, it is essential to elu...

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Bibliographic Details
Main Authors: Muhammad Asyaari Zakaria, Amnani Aminuddin, Nor Fadilah Rajab, Siti Fathiah Masre, Eng, Wee Chua
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2025
Online Access:http://journalarticle.ukm.my/25213/
http://journalarticle.ukm.my/25213/1/SMD%2018.pdf
Description
Summary:Lung squamous cell carcinoma (LUSC) is a deadly cancer, characterized by its complex genetic profiles. Additionally, the molecular mechanisms and etiology underlying LUSC growth are less extensively characterized as compared to adenocarcinoma subtype of lung cancer. Therefore, it is essential to elucidate the molecular mechanisms of LUSC in vivo and by using the human database to understand the disease. A LUSC BALB/c mice model was established using N-nitroso-tris-chloroethylurea (NTCU). After termination of mice, the lung tissues were subjected to RNA sequencing, followed by gene set enrichment analysis (GSEA) to identify the enriched pathways. Subsequently, the pathogenic single nucleotide polymorphism (SNP) was determined and enriched using g:Profiler. The transcriptomic profile of human LUSC patients was obtained and analyzed from The International Cancer Genome Consortium (ICGC). The impact of pathogenic simple somatic mutation (SSM) in human LUSC was determined using the Combined Annotation Dependent Depletion (CADD) score, which was also enriched using g:Profiler. Additionally, the enriched pathway of ‘Treatment-responsive’ was compared with ‘Non-responsive’ LUSC patients’ post-treatment. All pathway analysis was referred to the Reactome database, and an adjusted p-value ≤ 0.05 was considered statistically significant. The top pathway enriched in both mice and human LUSC showed that cholesterol, cellular interaction, immune system, and collagen were significantly affected. Briefly, this study identified important biological pathways that may contribute to LUSC development and hold potential as targets for LUSC therapy in the future.