The Prognosis of Lipid Reprogramming With Rosuvastatin, in Castrated Egyptian Prostate Cancer Patients
The Prognosis of Lipid Reprogramming With Rosuvastatin, in Castrated Egyptian Prostate Cancer Patients
Aim: 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.

 Methods: A total of 70 newly diagnosed castrated mPC patients treated with castration were
 recruited and divided into two groups: Group I included 30 patients and served as control
 (statin non-users) while group II included 40 patients 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, lipid profile (LDL, HDL, triglycerides and cholesterol)
 and lipid metabolism related markers (aldoketoreductase (AKR1C4), HMGCoA reductase, ABCA1,
 and SLDL RP1) were measured at baseline, after 3 and 6 months. Overall survival (OS) were
 analyzed by Kaplan-Meier and COX regression for prognostic significance.
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 Blood samples were withdrawn from all patients at baseline to monitor parameters under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 Then, blood samples were withdrawn from the two groups after 3 and 6 months.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.
Inclusion Criteria:

 -  Naïve newly diagnosed with metastatic prostate cancer

 -  Age ≥ 50 years.

 -  No psychological or geographical barriers for regular follow up of the patients.

 Exclusion Criteria:

 -  Age < 50 years.

 -  psychological or geographical barriers for regular follow up of the patients.