| Title: |
Up-regulation of intra-tumour LDLR gene expression is associated with statin treatment and better prostate cancer prognosis |
| Authors: |
Fonfara, Kia Eistrup; Fredsøe, Jacob; Ulhøi, Benedicte; Borgquist, Signe; Borre, Michael; Sørensen, Karina Dalsgaard |
| Source: |
Fonfara, K E, Fredsøe, J, Ulhøi, B, Borgquist, S, Borre, M & Sørensen, K D 2025, 'Up-regulation of intra-tumour LDLR gene expression is associated with statin treatment and better prostate cancer prognosis', Acta oncologica (Stockholm, Sweden), vol. 64, pp. 1371-1380. https://doi.org/10.2340/1651-226X.2025.43788 |
| Publication Year: |
2025 |
| Collection: |
Aarhus University: Research |
| Subject Terms: |
Aged; Biomarkers; Tumor/genetics; Gene Expression Profiling; Gene Expression Regulation; Neoplastic/drug effects; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use; Male; Middle Aged; Prognosis; Prostatectomy; Prostatic Neoplasms/genetics; Receptors; LDL/genetics; Up-Regulation; low-density lipoprotein receptor; simvastatin; atorvastatin; cholesterol; differential expression analysis |
| Description: |
BACKGROUND: Several studies have reported associations between statin treatment and a more favourable prognosis in prostate cancer (PC) patients. The underlying biology, however, has not been fully investigated. OBJECTIVE: To perform whole-transcriptome profiling of prostate tumour samples from PC patients to identify gene expression patterns and molecular pathways that may be associated with statin treatment. Furthermore, to investigate correlations between statin-associated gene expression changes and clinical outcomes. MATERIAL AND METHODS: We performed messenger Ribonucleic Acid (mRNA) sequencing on radical prostatectomy specimens from 186 patients with clinically-localised PC. The final dataset included 93 statin-users (93 PC and 43 adjacent normal [AN] samples) and 93 non-users (93 PC and 43 AN samples). We performed Differential Expression Analysis and Gene Set Enrichment Analysis (GSEA) between statin-users and non-users. Genes of interest were included in uni- and multivariate analyses exploring time to Biochemical Recurrence (BCR). RESULTS: Comparing statin-users and non-users, there were zero significantly differentially expressed genes (DEGs) in AN samples and 163 DEGs in PC samples. In statin-users, GSEA revealed downregulation of pathways known to drive PC aggressiveness, most significantly epithelial-mesenchymal transition. Low-density Lipoprotein Receptor (LDLR) was among the top-upregulated genes and expressed higher in atorvastatin than in simvastatin users. The LDLR upregulation was associated with prolonged BCR-free survival. INTERPRETATION: We identified several genes and pathways in PC tissue potentially associated with the reported beneficial effects of statin treatment in PC. Specifically, we identified an association between statin treatment and intra-tumour LDLR upregulation. This study contributes to the understanding of statin-mediated effects on PC. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0284-186X; 1100-1704 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41055203; info:eu-repo/semantics/altIdentifier/pissn/0284-186X; info:eu-repo/semantics/altIdentifier/eissn/1100-1704 |
| DOI: |
10.2340/1651-226X.2025.43788 |
| Availability: |
https://pure.au.dk/portal/en/publications/228c7a09-8adf-49a7-8089-d7a71cb6cb03; https://doi.org/10.2340/1651-226X.2025.43788; https://www.scopus.com/pages/publications/105017931440 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.C72B1561 |
| Database: |
BASE |