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Cholesterol Synthesis Pathway Genes in Prostate Cancer are consistently downregulated when tissue confounding is minimized
Open accessPreprint — published as 10.1186/s12885-018-4373-y · Paper page
Abstract
The relationship between cholesterol and prostate cancer has been extensively studied for decades, where high levels of cellular cholesterol are generally associated with cancer progression and less favorable outcomes. However, the role of in vivo cellular cholesterol synthesis in this process is unclear, and data on the transcriptional activity of cholesterol synthesis pathway genes in tissue from prostate cancer patients are inconsistent. A common problem with cancer tissue data from patient cohorts is the presence of heterogeneous tissue which confounds molecular analysis of the samples. In this study we present a method to minimize systematic confounding from stroma tissue in seven patient cohorts consisting of 1713 prostate cancer and 230 normal tissue samples. When confounding was minimized, differential gene expression analysis over all cohorts showed robust and consistent downregulation of nearly all genes in the cholesterol synthesis pathway. Additional analysis also identified cholesterol synthesis as the most significantly altered metabolic pathway in prostate cancer. This surprising observation is important for our understanding of how prostate cancer cells regulate cholesterol levels in vivo. Moreover, we show that tissue heterogeneity explains the lack of consistency in previous expression analysis of cholesterol synthesis genes in prostate cancer.
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Metadata
- Authors
- Rye, M. B., Bertilsson, H., Andersen, M. K., Rise, K., Bathen, T. F., Drabløs, F., & Tessem, M.-B.
- Affiliations
- Norwegian University of Science and Technology (NO)
- Corresponding author
- Rye, Morten Beck
- Venue
- BMC Cancer
- Publisher
- openRxiv
- Published
- 2017-11-17
- Volume
- 18
- Issue
- 1
- Pages
- 478-478
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC5922022
- OpenAlex
- W2769733322
- Cited by
- 21
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 2
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Cancer (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, 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)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- U.S. Department of Defense (W81XWH-11-1-, W81XWH, W81XWH1110520, W81XWH1110331)
- Kreftforeningen (100792–2013, 100792, grant100792-2013)
- Norges Teknisk-Naturvitenskapelige Universitet
- Helse Midt-Norge
- National Institutes of Health (W81XWH)
- National Cancer Institute (R01CA132874, U01CA111275, P50CA069568)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Keywords
- prostate cancer, cholesterol synthesis pathway, tissue heterogeneity, prostate stroma, gene downregulation, differential gene expression
- MeSH terms
- Cholesterol, Humans, Male, Models, Biological, Prostatic Neoplasms, Transcription, Genetic, Reproducibility of Results, Cohort Studies, Down-Regulation, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Stromal Cells, Lipid Metabolism, Biosynthetic Pathways
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