Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer
Open accessAbstract
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.
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This study discovered key factors in the gene-metabolite interaction network, metabolites, cell cycle genes and p53 signalling pathway genes that may have important roles in disease mechanisms.
“Furthermore, this study led to the discovery of key factors in the gene–metabolite interaction network, metabolites, cell cycle genes and genes of the p53 signalling pathway, which may have important roles in disease mechanisms.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [159]
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References 35 · Cited by 39
- Authors
- Hoang, L. T., Domingo‐Sabugo, C., Starren, E. S., Willis‐Owen, S. A. G., Morris‐Rosendahl, D. J., Nicholson, A. G., Cookson, W. O. C. M., & Moffatt, M. F.
- Affiliations
- Imperial College London (GB)
- Clinical Genetics and Genomics Royal Brompton and Harefield NHS Foundation Trust London UK
- Royal Brompton & Harefield NHS Foundation Trust (GB)
- Corresponding author
- Cookson, William O. C. M.
- Moffatt, Miriam F.
- ORCID
- Venue
- Molecular Oncology
- Publisher
- Wiley
- Published
- 2019-09-30
- Volume
- 13
- Issue
- 11
- Pages
- 2406-2421
- ISSN
- 1574-7891 (ISSN-L)
- 1878-0261
- PMC
- PMC6822241
- OpenAlex
- W2970572763
- Cited by
- 39
- References
- 35
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 9 · 2022: 7 · 2021: 7 · 2020: 3 · 2018: 1
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Royal Brompton and Harefield NHS Foundation Trust
- National Institute for Health and Care Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- non-small cell lung cancer, adenosine diphosphate, hemostasis, platelet activation, angiogenesis, Warburg effect, lung squamous cell carcinoma, lung adenocarcinoma, cancer metabolism, metastasis, therapeutic target, multi-omics integration
- MeSH terms
- Adenosine Diphosphate, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Hemostasis, Humans, Lung Neoplasms, Male, Middle Aged, RNA, Messenger, Signal Transduction, Platelet Activation, Gene Expression Profiling, Gene Regulatory Networks, Metabolomics, Metabolome, Gene Ontology
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