Up-regulation of intra-tumour LDLR gene expression is associated with statin treatment and better prostate cancer prognosis
DOI:
https://doi.org/10.2340/1651-226X.2025.43788Keywords:
Atorvastatin, Simvastatin, Cholesterol, Differential Expression Analysis, Low Density Lipoprotein ReceptorAbstract
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.
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Copyright (c) 2025 Kia Eistrup Fonfara, Jacob Fredsøe, Benedicte Parm Ulhøi, Signe Borgquist, Michael Borre, Karina Dalsgaard Sørensen
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