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Cited by 21Cancer, Lipids, and MetabolismCholesterol and Lipid MetabolismProstate Cancer Treatment and Research

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Cholesterol synthesis pathway genes in prostate cancer are transcriptionally downregulated when tissue confounding is minimized

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Rye, Morten Beck, Bertilsson, Helena, Andersen, Maria K., Rise, Kjersti, Bathen, Tone F., Drabløs, Finn, Tessem, May-Britt·2018·BMC Cancer
DOI 10.1186/s12885-018-4373-yPMC PMC5922022

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Abstract

BACKGROUND: 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. METHODS: 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 general method to minimize systematic confounding from stroma tissue in any prostate cancer cohort comparing prostate cancer and normal samples. In particular we use samples assessed by histopathology to identify genes enriched and depleted in prostate stroma. These genes are then used to assess stroma content in tissue samples from other prostate cancer cohorts where no histopathology is available. Differential expression analysis is performed by comparing cancer and normal samples where the average stroma content has been balanced between the sample groups. In total we analyzed seven patient cohorts with prostate cancer consisting of 1713 prostate cancer and 230 normal tissue samples. RESULTS: When stroma 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 Gene Ontology analysis also identified cholesterol synthesis as the most significantly altered metabolic pathway in prostate cancer at the transcriptional level. CONCLUSION: The surprising observation that cholesterol synthesis genes are downregulated in prostate cancer 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
ORCID
Venue
BMC Cancer
Publisher
Springer Science and Business Media LLC
Published
2018-04-27
Volume
18
Issue
1
Pages
478-478
ISSN
1471-2407 (ISSN-L)
DOI
10.1186/s12885-018-4373-y
PMC
PMC5922022
OpenAlex
W2769733322
Cited by
21
References
3
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
Licence
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
  • Samarbeidsorganet mellom Helse Midt-Norge RHF og NTNU
  • Kreftforeningen (grant100792-2013)
  • PhD position from strategic funding ISB, Norwegian University of Science and Technology NTNU
  • PhD position from Enabling Technologies, Norwegian University of Science and Technology
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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