Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer
Lung cancer is the leading cause of cancer‐related deaths in the world. The most prevalent subtype, accounting for 85% of cases, is non‐small‐cell lung cancer (NSCLC). Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the most common subtypes. Despite recent advances in treatmen...
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| Format: | Article |
| Language: | English |
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Wiley
2019-11-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.12568 |
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| author | Long T. Hoang Clara Domingo‐Sabugo Elizabeth S. Starren Saffron A.G. Willis‐Owen Deborah J. Morris‐Rosendahl Andrew G. Nicholson William O. C. M. Cookson Miriam F. Moffatt |
| author_facet | Long T. Hoang Clara Domingo‐Sabugo Elizabeth S. Starren Saffron A.G. Willis‐Owen Deborah J. Morris‐Rosendahl Andrew G. Nicholson William O. C. M. Cookson Miriam F. Moffatt |
| author_sort | Long T. Hoang |
| collection | DOAJ |
| description | Lung cancer is the leading cause of cancer‐related deaths in the world. The most prevalent subtype, accounting for 85% of cases, is non‐small‐cell lung cancer (NSCLC). Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the most common subtypes. Despite recent advances in treatment, the low 5‐year survival rate of NSCLC patients (approximately 13%) reflects the lack of early diagnostic biomarkers and incomplete understanding of the underlying disease mechanisms. We hypothesized that integration of metabolomic, transcriptomic and genetic profiles of tumours and matched normal tissues could help to identify important factors and potential therapeutic targets that contribute to tumorigenesis. We integrated omics profiles in tumours and matched adjacent normal tissues of patients with LUSC (N = 20) and LUAD (N = 17) using multiple system biology approaches. We confirmed the presence of previously described metabolic pathways in NSCLC, particularly those mediating the Warburg effect. In addition, through our combined omics analyses we found that metabolites and genes that contribute to haemostasis, angiogenesis, platelet activation and cell proliferation were predominant in both subtypes of NSCLC. The important roles of adenosine diphosphate in promoting cancer metastasis through platelet activation and angiogenesis suggest this metabolite could be a potential therapeutic target. |
| format | Article |
| id | doaj-art-4a9a508851924fa2ae8044e3fc1ee6d4 |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2019-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-4a9a508851924fa2ae8044e3fc1ee6d42024-11-23T12:01:00ZengWileyMolecular Oncology1574-78911878-02612019-11-0113112406242110.1002/1878-0261.12568Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancerLong T. Hoang0Clara Domingo‐Sabugo1Elizabeth S. Starren2Saffron A.G. Willis‐Owen3Deborah J. Morris‐Rosendahl4Andrew G. Nicholson5William O. C. M. Cookson6Miriam F. Moffatt7National Heart and Lung Institute Faculty of Medicine Imperial College London UKNational Heart and Lung Institute Faculty of Medicine Imperial College London UKNational Heart and Lung Institute Faculty of Medicine Imperial College London UKNational Heart and Lung Institute Faculty of Medicine Imperial College London UKClinical Genetics and Genomics Royal Brompton and Harefield NHS Foundation Trust London UKNational Heart and Lung Institute Faculty of Medicine Imperial College London UKNational Heart and Lung Institute Faculty of Medicine Imperial College London UKNational Heart and Lung Institute Faculty of Medicine Imperial College London UKLung cancer is the leading cause of cancer‐related deaths in the world. The most prevalent subtype, accounting for 85% of cases, is non‐small‐cell lung cancer (NSCLC). Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the most common subtypes. Despite recent advances in treatment, the low 5‐year survival rate of NSCLC patients (approximately 13%) reflects the lack of early diagnostic biomarkers and incomplete understanding of the underlying disease mechanisms. We hypothesized that integration of metabolomic, transcriptomic and genetic profiles of tumours and matched normal tissues could help to identify important factors and potential therapeutic targets that contribute to tumorigenesis. We integrated omics profiles in tumours and matched adjacent normal tissues of patients with LUSC (N = 20) and LUAD (N = 17) using multiple system biology approaches. We confirmed the presence of previously described metabolic pathways in NSCLC, particularly those mediating the Warburg effect. In addition, through our combined omics analyses we found that metabolites and genes that contribute to haemostasis, angiogenesis, platelet activation and cell proliferation were predominant in both subtypes of NSCLC. The important roles of adenosine diphosphate in promoting cancer metastasis through platelet activation and angiogenesis suggest this metabolite could be a potential therapeutic target.https://doi.org/10.1002/1878-0261.12568ADPgeneticshaemostasismetabolomicNSCLCplatelet activation |
| spellingShingle | Long T. Hoang Clara Domingo‐Sabugo Elizabeth S. Starren Saffron A.G. Willis‐Owen Deborah J. Morris‐Rosendahl Andrew G. Nicholson William O. C. M. Cookson Miriam F. Moffatt Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer Molecular Oncology ADP genetics haemostasis metabolomic NSCLC platelet activation |
| title | Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer |
| title_full | Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer |
| title_fullStr | Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer |
| title_full_unstemmed | Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer |
| title_short | Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer |
| title_sort | metabolomic transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non small cell lung cancer |
| topic | ADP genetics haemostasis metabolomic NSCLC platelet activation |
| url | https://doi.org/10.1002/1878-0261.12568 |
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