The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial

• Published in: PloS one Vol. 17; no. 12; p. e0278282
• Main Authors: Karkeet, Riham M, Zekri, Abdelrahman N, Sayed-Ahmed, Mohamed M, Sherif, Ghada M, Salem, Salem E, Abdelbary, Ahmed, Fouad, Mariam A, Saad, Sherif Y
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.12.2022; Public Library of Science (PLoS)
• Subjects: ABCA1 protein; Alkaline phosphatase; Androgens; Antigens; ATP-binding protein; Biology and Life Sciences; Care and treatment; Castration; Caveolin; Caveolin-1; Cholesterol; Disease; Dosage and administration; Egypt; Epidermal growth factor; Epidermal growth factor receptors; Genetics; Growth factors; Health aspects; High density lipoprotein; HMG-CoA reductase inhibitors; Humans; Hydroxymethylglutaryl-CoA reductase; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Lipid metabolism; Lipids; Low density lipoprotein; Low density lipoprotein receptors; Male; Medical prognosis; Medicine and Health Sciences; Metabolism; Metastases; Metastasis; Mortality; Oxidoreductases; Patients; Plasma; Prognosis; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - surgery; Receptor density; Receptors; Reductases; Rosuvastatin; Rosuvastatin Calcium - therapeutic use; Sample size; Smoking; Statins; Survival; Survival analysis; Triglycerides; Egypt
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0278282

The role of surgical castration and rosuvastatin treatment on lipid profile and lipid metabolism related markers was evaluated for their prognostic significance in metastatic prostate cancer (mPC) patients. A total of 84 newly diagnosed castrated mPC patients treated with castration were recruited and divided into two groups: Group I served as control (statin non-users) while group II treated with Rosuvastatin (20 mg/day) for 6 months and served as statin users. Prostate specific antigen (PSA), epidermal growth factor receptor (EGFR), Caveolin-1 (CAV1), lipid profile (LDL, HDL, triglycerides (TG) and total cholesterol (TC)) and lipid metabolism related markers (aldoketoreductase (AKR1C4), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter A1 (ABCA1), and soluble low density lipoprotein receptor related protein 1 (SLDLRP1)) were measured at baseline, after 3 and 6 months. Overall survival (OS) was analyzed by Kaplan-Meier and COX regression for prognostic significance. Before castration, HMG-CoA reductase was elevated in patients <65 years (P = 0.009). Bone metastasis was associated with high PSA level (P = 0.013), but low HMGCR (P = 0.004). Patients with positive family history for prostate cancer showed high levels of EGFR, TG, TC, LDL, alkaline phosphatase (ALP), but low AKR1C4, SLDLRP1, CAV1 and ABCA-1 levels. Smokers had high CAV1 level (P = 0.017). After 6 months of castration and rosuvastatin administration, PSA, TG, LDL and TC were significantly reduced, while AKR1C4, HMGCR, SLDLRP1, CAV1 and ABCA-1 were significantly increased. Overall survival was reduced in patients with high baseline of SLDLRP1 (>3385 pg/ml, P = 0.001), PSA (>40 ng/ml, P = 0.003) and CAV1 (>4955 pg/ml, P = 0.021). Results of the current study suggest that the peripheral lipidogenic effects of rosuvastatin may have an impact on the treatment outcome and survival of castrated mPC patients. This trial was registered at the Pan African Clinical Trial Registry with identification number PACTR202102664354163 and at ClinicalTrials.gov with identification number NCT04776889.