ArticleBMC cancer2018
Cholesterol synthesis pathway genes in prostate cancer are transcriptionally downregulated when tissue confounding is minimized.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Obesogens in Prostate Cancer: An Endocrine and Metabolic Threat.Current obesity reports · 2026Review
- Spatial integration of multi-omics data from serial sections using the novel Multi-Omics Imaging Integration Toolset.GigaScience · 2025Article
- Article
- Combining Molecular Subtypes with Multivariable Clinical Models Has the Potential to Improve Prediction of Treatment Outcomes in Prostate Cancer at Diagnosis.Current oncology (Toronto, Ont.) · 2022Article
- Article
- From Omics to Multi-Omics Approaches for In-Depth Analysis of the Molecular Mechanisms of Prostate Cancer.International journal of molecular sciences · 2022Review
- Prostate Cancer-Focus on Cholesterol.Cancers · 2021Review
- HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma.PLoS biology · 2021Article
- Using the Method of "Optical Biopsy" of Prostatic Tissue to Diagnose Prostate Cancer.Molecules (Basel, Switzerland) · 2021Article
- Spatial modeling of prostate cancer metabolic gene expression reveals extensive heterogeneity and selective vulnerabilities.Scientific reports · 2020Article
- DNA hypermethylation associated with upregulated gene expression in prostate cancer demonstrates the diversity of epigenetic regulation.BMC medical genomics · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe 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.
methodsA 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.
resultsWhen 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.
conclusionThe 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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