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In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer
SIMPLE SUMMARY: The present study identified a panel of transcripts involved in the pathogenesis of both severe asthma and lung cancer. The genes identified using publicly available transcriptomics data were validated on cell lines, plasma samples, and archival tissue biopsies from asthmatic and lun...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996975/ https://www.ncbi.nlm.nih.gov/pubmed/35406434 http://dx.doi.org/10.3390/cancers14071663 |
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author | Salameh, Laila Bhamidimarri, Poorna Manasa Saheb Sharif-Askari, Narjes Dairi, Youssef Hammoudeh, Sarah Musa Mahdami, Amena Alsharhan, Mouza Tirmazy, Syed Hammad Rawat, Surendra Singh Busch, Hauke Hamid, Qutayba Al Heialy, Saba Hamoudi, Rifat Mahboub, Bassam |
author_facet | Salameh, Laila Bhamidimarri, Poorna Manasa Saheb Sharif-Askari, Narjes Dairi, Youssef Hammoudeh, Sarah Musa Mahdami, Amena Alsharhan, Mouza Tirmazy, Syed Hammad Rawat, Surendra Singh Busch, Hauke Hamid, Qutayba Al Heialy, Saba Hamoudi, Rifat Mahboub, Bassam |
author_sort | Salameh, Laila |
collection | PubMed |
description | SIMPLE SUMMARY: The present study identified a panel of transcripts involved in the pathogenesis of both severe asthma and lung cancer. The genes identified using publicly available transcriptomics data were validated on cell lines, plasma samples, and archival tissue biopsies from asthmatic and lung cancer patients. The functional roles of the identified markers in both the diseases were ascertained from the literature. These molecular markers might be useful for diagnosing lung cancer at early stages. ABSTRACT: Severe asthma and lung cancer are both heterogeneous pathological diseases affecting the lung tissue. Whilst there are a few studies that suggest an association between asthma and lung cancer, to the best of our knowledge, this is the first study to identify common genes involved in both severe asthma and lung cancer. Publicly available transcriptomic data for 23 epithelial brushings from severe asthmatics and 55 samples of formalin-fixed paraffin-embedded (FFPE) lung cancer tissue at relatively early stages were analyzed by absolute gene set enrichment analysis (GSEA) in comparison to 37 healthy bronchial tissue samples. The key pathways enriched in asthmatic patients included adhesion, extracellular matrix, and epithelial cell proliferation, which contribute to tissue remodeling. In the lung cancer dataset, the main pathways identified were receptor tyrosine kinase signaling, wound healing, and growth factor response, representing the early cancer pathways. Analysis of the enriched genes derived from the pathway analysis identified seven genes expressed in both the asthma and lung cancer sets: BCL3, POSTN, PPARD, STAT1, MYC, CD44, and FOSB. The differential expression of these genes was validated in vitro in the cell lines retrieved from different lung cancer and severe asthma patients using real-time PCR. The effect of the expression of the seven genes identified in the study on the overall survival of lung cancer patients (n = 1925) was assessed using a Kaplan–Meier plot. In vivo validation performed in the archival biopsies obtained from patients diagnosed with both the disease conditions provided interesting insights into the pathogenesis of severe asthma and lung cancer, as indicated by the differential expression pattern of the seven transcripts in the mixed group as compared to the asthmatics and lung cancer samples alone. |
format | Online Article Text |
id | pubmed-8996975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89969752022-04-12 In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer Salameh, Laila Bhamidimarri, Poorna Manasa Saheb Sharif-Askari, Narjes Dairi, Youssef Hammoudeh, Sarah Musa Mahdami, Amena Alsharhan, Mouza Tirmazy, Syed Hammad Rawat, Surendra Singh Busch, Hauke Hamid, Qutayba Al Heialy, Saba Hamoudi, Rifat Mahboub, Bassam Cancers (Basel) Article SIMPLE SUMMARY: The present study identified a panel of transcripts involved in the pathogenesis of both severe asthma and lung cancer. The genes identified using publicly available transcriptomics data were validated on cell lines, plasma samples, and archival tissue biopsies from asthmatic and lung cancer patients. The functional roles of the identified markers in both the diseases were ascertained from the literature. These molecular markers might be useful for diagnosing lung cancer at early stages. ABSTRACT: Severe asthma and lung cancer are both heterogeneous pathological diseases affecting the lung tissue. Whilst there are a few studies that suggest an association between asthma and lung cancer, to the best of our knowledge, this is the first study to identify common genes involved in both severe asthma and lung cancer. Publicly available transcriptomic data for 23 epithelial brushings from severe asthmatics and 55 samples of formalin-fixed paraffin-embedded (FFPE) lung cancer tissue at relatively early stages were analyzed by absolute gene set enrichment analysis (GSEA) in comparison to 37 healthy bronchial tissue samples. The key pathways enriched in asthmatic patients included adhesion, extracellular matrix, and epithelial cell proliferation, which contribute to tissue remodeling. In the lung cancer dataset, the main pathways identified were receptor tyrosine kinase signaling, wound healing, and growth factor response, representing the early cancer pathways. Analysis of the enriched genes derived from the pathway analysis identified seven genes expressed in both the asthma and lung cancer sets: BCL3, POSTN, PPARD, STAT1, MYC, CD44, and FOSB. The differential expression of these genes was validated in vitro in the cell lines retrieved from different lung cancer and severe asthma patients using real-time PCR. The effect of the expression of the seven genes identified in the study on the overall survival of lung cancer patients (n = 1925) was assessed using a Kaplan–Meier plot. In vivo validation performed in the archival biopsies obtained from patients diagnosed with both the disease conditions provided interesting insights into the pathogenesis of severe asthma and lung cancer, as indicated by the differential expression pattern of the seven transcripts in the mixed group as compared to the asthmatics and lung cancer samples alone. MDPI 2022-03-25 /pmc/articles/PMC8996975/ /pubmed/35406434 http://dx.doi.org/10.3390/cancers14071663 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Salameh, Laila Bhamidimarri, Poorna Manasa Saheb Sharif-Askari, Narjes Dairi, Youssef Hammoudeh, Sarah Musa Mahdami, Amena Alsharhan, Mouza Tirmazy, Syed Hammad Rawat, Surendra Singh Busch, Hauke Hamid, Qutayba Al Heialy, Saba Hamoudi, Rifat Mahboub, Bassam In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer |
title | In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer |
title_full | In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer |
title_fullStr | In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer |
title_full_unstemmed | In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer |
title_short | In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer |
title_sort | in silico bioinformatics followed by molecular validation using archival ffpe tissue biopsies identifies a panel of transcripts associated with severe asthma and lung cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996975/ https://www.ncbi.nlm.nih.gov/pubmed/35406434 http://dx.doi.org/10.3390/cancers14071663 |
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