Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach
Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.
Authors
- Beata Świątkowska (ORCID: https://orcid.org/0000-0003-3757-3868)
- Jolanta Lissowska (ORCID: https://orcid.org/0000-0003-2695-5799)
- Hanla A. Park (ORCID: https://orcid.org/0000-0001-8055-3729)
- Давид Заридзе (ORCID: https://orcid.org/0000-0002-2824-3704)
- S. Senkin (ORCID: https://orcid.org/0000-0001-5848-005X)
- Vincent Cahais (ORCID: https://orcid.org/0000-0001-5530-4368)
- Joshua Atkins (ORCID: https://orcid.org/0000-0003-0821-1112)
- Ivana Holcátová (ORCID: https://orcid.org/0000-0002-1366-0337)
- Cyrille Cuenin
- V. Janout (ORCID: https://orcid.org/0000-0003-1594-3901)
- Nicolas Alcala (ORCID: https://orcid.org/0000-0002-5961-5064)
- Ghislaine Scélo (ORCID: https://orcid.org/0000-0002-2692-8507)
- Amélie Chabrier
- Ricardo Cortez Cardoso Penha (ORCID: https://orcid.org/0000-0002-2847-1993)
- Paul Brennan (ORCID: https://orcid.org/0000-0002-7977-6818)
- Simona Ognjanovic (ORCID: https://orcid.org/0000-0003-3412-2156)
- Karl Smith‐Byrne
- Zdenko Herceg (ORCID: https://orcid.org/0000-0003-4109-3154)
- Matthieu Foll (ORCID: https://orcid.org/0000-0001-9006-8436)
- James McKay (ORCID: https://orcid.org/0000-0002-1787-3874)
- Anna Horňáková (ORCID: https://orcid.org/0000-0002-1024-8056)
- Slaviša Savić (ORCID: https://orcid.org/0000-0002-3635-7437)
- Alexandra Sexton Oates
- Anush Mukeria
Institutions
- Nofer Institute of Occupational Medicine (PL)
- Charles University (CZ)
- University of Oxford (GB)
- Russian Cancer Research Center NN Blokhin (RU)
- University Hospital Center Dr Dragiša Mišović (RS)
- National Institute Of Hygiene And Epidemiology (VN)
- Observational & Pragmatic Research Institute (SG)
- National Institute of Oncology (HU)
- The Maria Sklodowska-Curie National Research Institute of Oncology (PL)
- Cancer Research UK Oxford Centre (GB)
- Centre international de recherche sur le cancer (FR)
- Palacký University Olomouc (CZ)
Publication Details
- Journal
- Molecular Systems Biology
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1038/s44320-024-00072-3
- Citations
- 4
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Centre International de Recherche sur le Cancer
- Cancer Research UK
- Institut National Du Cancer
- National Institutes of Health
- National Cancer Institute