The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-Trial
Background: Prostate cancer (PCa) remains a global health burden, with limited reliable biomarkers beyond prostate-specific antigen (PSA). Statins have been associated with survival benefits in advanced Pca, potentially by modulating cholesterol metabolism and tumor biology. However, the causal mech...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000119 |
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| author | Eemil Lehtonen Maiju Vertanen Heimo Syvälä Teemu Tolonen Seppo Auriola Teuvo Tammela Aino Siltari Teemu Murtola |
| author_facet | Eemil Lehtonen Maiju Vertanen Heimo Syvälä Teemu Tolonen Seppo Auriola Teuvo Tammela Aino Siltari Teemu Murtola |
| author_sort | Eemil Lehtonen |
| collection | DOAJ |
| description | Background: Prostate cancer (PCa) remains a global health burden, with limited reliable biomarkers beyond prostate-specific antigen (PSA). Statins have been associated with survival benefits in advanced Pca, potentially by modulating cholesterol metabolism and tumor biology. However, the causal mechanisms are not well understood. A distinct three-lipid signature (3LS) has previously been proposed as a prognostic biomarker for PCa. Objective: This study investigates the effects of atorvastatin intervention on PCa tissue markers, long-term clinical outcomes, and the prognostic value of the 3LS derived from prostate tissue lipidome. Methods: The ESTO1 trial randomized 158 statin-naïve PCa patients to receive high-dose atorvastatin (80 mg daily) or placebo before prostatectomy. Long term outcomes were assessed for 102 patients through medical records review. Prostate tissue samples were pathologically characterized, and lipidome quantified. Cox regression models were used to analyse clinical outcomes between the groups. The 3LS score was calculated by identifying the constituent lipids from the prostate lipidome. Findings: Higher intraprostatic atorvastatin lactone concentrations were associated with reduced Ki67 expression and PSA levels. After a median follow-up of seven years, no significant differences were observed in biochemical recurrence, overall mortality, or initiation of hormonal therapy. However, the atorvastatin arm had a lower risk of major acute cardiovascular events (HR 0.11, 95% CI 0.01–1.01). The intraprostatic 3LS correlated with higher baseline tumor aggressiveness but did not predict subsequent outcomes. Conclusion: Higher atorvastatin lactone concentrations in the prostate tissue were linked to improved pathological variables. Pre-surgery statin intervention reduced MACE risk but no impact on other clinical outcomes was observed. The 3LS from prostate tissue does not seem to be prognostic marker in localized Pca. |
| format | Article |
| id | doaj-art-523d054d54c742829808584eb2123938 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-523d054d54c742829808584eb21239382025-02-08T04:59:59ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-03-0161101132The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-TrialEemil Lehtonen0Maiju Vertanen1Heimo Syvälä2Teemu Tolonen3Seppo Auriola4Teuvo Tammela5Aino Siltari6Teemu Murtola7Faculty of Medicine and Health Technology, Tampere University, Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandTampere University, Faculty of Medicine and Health Technology, Tampere, Finland; Department of Pathology, FimLab Laboratories, Tampere, FinlandSchool of Pharmacy, University of Eastern Finland, Kuopio, FinlandTampere University, Faculty of Medicine and Health Technology, Tampere, Finland; TAYS Cancer Center, Department of Urology, Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, Finland; TAYS Cancer Center, Department of Urology, Tampere, Finland; Corresponding author at: Faculty of Medicine and Health Technology, Tampere University, Biokatu 6, 33521 Tampere, Finland. Tel: +358 3 3116 5015.Background: Prostate cancer (PCa) remains a global health burden, with limited reliable biomarkers beyond prostate-specific antigen (PSA). Statins have been associated with survival benefits in advanced Pca, potentially by modulating cholesterol metabolism and tumor biology. However, the causal mechanisms are not well understood. A distinct three-lipid signature (3LS) has previously been proposed as a prognostic biomarker for PCa. Objective: This study investigates the effects of atorvastatin intervention on PCa tissue markers, long-term clinical outcomes, and the prognostic value of the 3LS derived from prostate tissue lipidome. Methods: The ESTO1 trial randomized 158 statin-naïve PCa patients to receive high-dose atorvastatin (80 mg daily) or placebo before prostatectomy. Long term outcomes were assessed for 102 patients through medical records review. Prostate tissue samples were pathologically characterized, and lipidome quantified. Cox regression models were used to analyse clinical outcomes between the groups. The 3LS score was calculated by identifying the constituent lipids from the prostate lipidome. Findings: Higher intraprostatic atorvastatin lactone concentrations were associated with reduced Ki67 expression and PSA levels. After a median follow-up of seven years, no significant differences were observed in biochemical recurrence, overall mortality, or initiation of hormonal therapy. However, the atorvastatin arm had a lower risk of major acute cardiovascular events (HR 0.11, 95% CI 0.01–1.01). The intraprostatic 3LS correlated with higher baseline tumor aggressiveness but did not predict subsequent outcomes. Conclusion: Higher atorvastatin lactone concentrations in the prostate tissue were linked to improved pathological variables. Pre-surgery statin intervention reduced MACE risk but no impact on other clinical outcomes was observed. The 3LS from prostate tissue does not seem to be prognostic marker in localized Pca.http://www.sciencedirect.com/science/article/pii/S1476558625000119Prostate cancerStatinsLipidomicsThree-lipid signatureKi67Biochemical recurrence |
| spellingShingle | Eemil Lehtonen Maiju Vertanen Heimo Syvälä Teemu Tolonen Seppo Auriola Teuvo Tammela Aino Siltari Teemu Murtola The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-Trial Neoplasia: An International Journal for Oncology Research Prostate cancer Statins Lipidomics Three-lipid signature Ki67 Biochemical recurrence |
| title | The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-Trial |
| title_full | The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-Trial |
| title_fullStr | The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-Trial |
| title_full_unstemmed | The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-Trial |
| title_short | The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-Trial |
| title_sort | impact of atorvastatin on intraprostatic biomarkers prognostic value of 3ls score follow up of esto1 trial |
| topic | Prostate cancer Statins Lipidomics Three-lipid signature Ki67 Biochemical recurrence |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000119 |
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