ArticleActa oncologica (Stockholm, Sweden)2025
Up-regulation of intra-tumour LDLR gene expression is associated with statin treatment and better prostate cancer prognosis.
Article in Acta oncologica (Stockholm, Sweden), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSeveral 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.
objectiveTo 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
methodsWe 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).
resultsComparing 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.
interpretationWe 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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