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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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
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author Muhammad Asyaari Zakaria,
Amnani Aminuddin,
Nor Fadilah Rajab,
Siti Fathiah Masre,
Eng, Wee Chua
author_facet Muhammad Asyaari Zakaria,
Amnani Aminuddin,
Nor Fadilah Rajab,
Siti Fathiah Masre,
Eng, Wee Chua
author_sort Muhammad Asyaari Zakaria,
building UKM Institutional Repository
collection Online Access
description 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.
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spelling oai:generic.eprints.org:252132025-05-13T07:51:56Z http://journalarticle.ukm.my/25213/ Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients Muhammad Asyaari Zakaria, Amnani Aminuddin, Nor Fadilah Rajab, Siti Fathiah Masre, Eng, Wee Chua 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. Penerbit Universiti Kebangsaan Malaysia 2025 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/25213/1/SMD%2018.pdf Muhammad Asyaari Zakaria, and Amnani Aminuddin, and Nor Fadilah Rajab, and Siti Fathiah Masre, and Eng, Wee Chua (2025) Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients. Sains Malaysiana, 54 (3). pp. 839-868. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol54num3_2025/contentsVol54num3_2025.html
spellingShingle Muhammad Asyaari Zakaria,
Amnani Aminuddin,
Nor Fadilah Rajab,
Siti Fathiah Masre,
Eng, Wee Chua
Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients
title Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients
title_full Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients
title_fullStr Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients
title_full_unstemmed Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients
title_short Potentially dysregulated cholesterol, cellular interaction, immune, and collagen in NTCU-induced lung squamous cell carcinoma in vivo and LUSC patients
title_sort potentially dysregulated cholesterol, cellular interaction, immune, and collagen in ntcu-induced lung squamous cell carcinoma in vivo and lusc patients
url http://journalarticle.ukm.my/25213/
http://journalarticle.ukm.my/25213/
http://journalarticle.ukm.my/25213/1/SMD%2018.pdf