Back to Search
Start Over
Cholesterol synthesis pathway genes in prostate cancer are transcriptionally downregulated when tissue confounding is minimized
- Source :
- BMC Cancer, Vol 18, Iss 1, Pp 1-17 (2018), BMC Cancer
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
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. © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.
- Subjects :
- Male
0301 basic medicine
Cancer Research
medicine.medical_specialty
Transcription, Genetic
Down-Regulation
Stroma
Biology
Models, Biological
lcsh:RC254-282
Gene Expression Regulation, Enzymologic
Cohort Studies
03 medical and health sciences
Prostate cancer
chemistry.chemical_compound
Gene expression analysis
Surgical oncology
Prostate
Internal medicine
Gene expression
Genetics
medicine
Humans
RNA-Seq
HMGCR
GSEA
Cholesterol
Prostatic Neoplasms
Reproducibility of Results
Cancer
Lipid Metabolism
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Biosynthetic Pathways
3. Good health
Gene Expression Regulation, Neoplastic
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Oncology
chemistry
Cancer research
Tissue heterogeneity
Histopathology
Stromal Cells
Research Article
Subjects
Details
- ISSN :
- 14712407
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....da5a1b6d3824a3c927230447770551cc