This prospective randomized controlled study was conducted at the National Cancer Institute (NCI), Cairo University. The study ID BB1901-30303 was approved by the Institutional Human Research Ethics Committee of NCI, Egypt, Number 00004025, with IRB review Number 201819019.3 and conducted in accordance with the Declaration of Helsinki with informed consent was taken from all participants. The study included 70 Egyptian metastatic prostate cancer (m PC) patients who were treated and followed up in the NCI hospital in the period from January 2019 till December 2020. Patients were recruited from January to June 2019, then followed-up to December 2020.

Blood samples were withdrawn from all patients at baseline to monitor parameters under investigation. Then, all patients were subjected to surgical castration and divided in to two groups. Group I included 30 patients and served as control (statin non-users). Group II included 40 patients treated with Rosuvastatin (20 mg/day) for 6 months and served as statin users. Then, blood samples were withdrawn from the two groups after 3 and 6 months. Full demographic information and clinicopatholologic characteristics were obtained for each patient including; age, comorbid diseases, initial complain symptoms, family history of malignancy, smoking status and performance status. Also, serum level of prostate specific antigen (PSA) and alkaline phosphatase (ALP), Gleason score and metastasis sites were recorded. The treatment modality and decision making were according to NCI guidelines.

Collected whole blood samples into k.EDTA tubes were incubated at room temperature for 15 minutes and then centrifuged for 20 minutes at 1500 rpm. The plasma supernatant was carefully collected and freezed until analysis. Plasma protein concentrations of some lipid reprogramming and prostate cancer aggressiveness markers were measured. Kits were probed against human soluble low density lipoprotein receptor related protein -1 (SLDLRP-1; catalogue number: SL2705Hu), human ATP binding cassette transporter A-1 (ABCA-1; catalogue number: SL0314Hu), Human Aldoketo-reductase family 1 member C4 (AKR-1C4; catalogue number: SL3032Hu), human 3-hydroxy-3-methylglutaryl Co-enzyme A reductase (HMGCR; catalogue number: SL3030Hu), human epidermal growth factor receptor (EGFR; catalogue number: SL0665Hu) and human Caveolin-1 (Cav-1; catalogue number: SL0427Hu). Procedures were carried out in accordance with the manufacturer's instructions. The concentration of the markers in plasma samples was calculated by comparing the OD of the samples to the corresponding plotted standard curves.

Data management and statistical analysis were performed using The Statistical Package for Social Sciences (SPSS) version 24. Normal distribution and variance homogeneity of data were assessed using the Kolmogorov-Smirnov and Levene's tests, respectively. Numerical data were summarized using median and interquartile range (IQR). Categorical data were summarized as count and percentage. Patients were stratified according to their clinicopathological factors and for more than two subgroups of patients, the change in measured parameters were tested for significance using Kruskal-Wallis test and the pairwise comparison were done using Mann-Whitney. The change in proteins concentration over time was tested using Friedman test of significance. Spearman correlation analysis was used to test all possible correlations. Kaplan- Meier survival analysis was used to calculate the cumulative survival rate as well as median levels of OS after two years of follow up. OS was calculated from date of diagnosis to date of death by any cause. Living patients or patients lost to follow-up were censored on the last known alive date. The hazardous effect of death or progression Cox proportion hazard Model was used to evaluate the hazardous effect of different clinicopathological and proteins levels on death and progression. All P-values are two-sided. P-values \< 0.05 were considered significant.