In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer
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 asth...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/7/1663 |
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| author | Laila Salameh Poorna Manasa Bhamidimarri Narjes Saheb Sharif-Askari Youssef Dairi Sarah Musa Hammoudeh Amena Mahdami Mouza Alsharhan Syed Hammad Tirmazy Surendra Singh Rawat Hauke Busch Qutayba Hamid Saba Al Heialy Rifat Hamoudi Bassam Mahboub |
| author_facet | Laila Salameh Poorna Manasa Bhamidimarri Narjes Saheb Sharif-Askari Youssef Dairi Sarah Musa Hammoudeh Amena Mahdami Mouza Alsharhan Syed Hammad Tirmazy Surendra Singh Rawat Hauke Busch Qutayba Hamid Saba Al Heialy Rifat Hamoudi Bassam Mahboub |
| author_sort | Laila Salameh |
| collection | DOAJ |
| description | 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: <i>BCL3</i>, <i>POSTN</i>, <i>PPARD</i>, <i>STAT1</i>, <i>MYC</i>, <i>CD44</i>, and <i>FOSB</i>. 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 (<i>n</i> = 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. |
| first_indexed | 2024-03-09T12:04:05Z |
| format | Article |
| id | doaj.art-d09adb99f1a04f37ada017a79a19c03d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T12:04:05Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d09adb99f1a04f37ada017a79a19c03d2023-11-30T23:00:15ZengMDPI AGCancers2072-66942022-03-01147166310.3390/cancers14071663In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung CancerLaila Salameh0Poorna Manasa Bhamidimarri1Narjes Saheb Sharif-Askari2Youssef Dairi3Sarah Musa Hammoudeh4Amena Mahdami5Mouza Alsharhan6Syed Hammad Tirmazy7Surendra Singh Rawat8Hauke Busch9Qutayba Hamid10Saba Al Heialy11Rifat Hamoudi12Bassam Mahboub13Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesDubai Health Authority, Dubai 4545, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesDubai Health Authority, Dubai 4545, United Arab EmiratesDubai Health Authority, Dubai 4545, United Arab EmiratesCollage of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab EmiratesLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck 23562, GermanySharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesCollage of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesDubai Health Authority, Dubai 4545, United Arab EmiratesSevere 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: <i>BCL3</i>, <i>POSTN</i>, <i>PPARD</i>, <i>STAT1</i>, <i>MYC</i>, <i>CD44</i>, and <i>FOSB</i>. 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 (<i>n</i> = 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.https://www.mdpi.com/2072-6694/14/7/1663asthmalung cancerGSEA analysisbioinformatics<i>POSTN</i><i>LUM</i> |
| spellingShingle | Laila Salameh Poorna Manasa Bhamidimarri Narjes Saheb Sharif-Askari Youssef Dairi Sarah Musa Hammoudeh Amena Mahdami Mouza Alsharhan Syed Hammad Tirmazy Surendra Singh Rawat Hauke Busch Qutayba Hamid Saba Al Heialy Rifat Hamoudi Bassam Mahboub In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer Cancers asthma lung cancer GSEA analysis bioinformatics <i>POSTN</i> <i>LUM</i> |
| 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 | asthma lung cancer GSEA analysis bioinformatics <i>POSTN</i> <i>LUM</i> |
| url | https://www.mdpi.com/2072-6694/14/7/1663 |
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