Abstract 3293: Serum and intraprostatic lipidome level shift during statin use among prostate cancer patients

Abstract

Abstract Prostate cancer patients using cholesterol-lowering statins have 30 % lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway which is active in prostate cancer cells. Statin intervention also causes lipidome level shift in the serum. However, it is unknown whether statin intervention also affects intraprostatic lipidome (IPL) as well. We studied the lipidome level shift among Finnish males diagnosed with prostate cancer and scheduled for radical prostatectomy in a randomized, placebo-controlled double-blind clinical trial. Total number of participants was 86 where 41 were given placebo and 45 were treated daily with 80 mg of atorvastatin (AS) for a median of 27 days preceeding the surgery. The serum lipidome (SL) level was measured before and after the intervention using mass spectrometer, whereas the IPL level was measured after the surgery. SL contains 213 lipid aggregates, while the IPL contains 4,652 single-molecule lipids. Furthermore, we investigated if the baseline lipidome level or the shift during intervention displays relationship with tumor Gleason grade, PSA level, Ki67 proliferation marker level in the tissue, and / or intraprostatic inflammation. The relationship was studied using supervised random forest classification (RFC), and linear regression (LR) adjusted for age and body mass index. RFC robustness with respect to the intrinsic randomization was measured by repeating RFC 100 times. The 4,652 IPL molecules were reduced to 101 after limiting analysis to ones demonstrating statistically significant difference between placebo and AS group. The statistically significant difference was tested with t-test and Mann-Whitney test depending on the sample distribution. The SL difference before-after intervention separates the two groups with extremely low RFC error of 8.1 – 9.3 %. This indicates that the intervention has systematically altered the SL. The RFC error for the IPL was 29 – 37.7 % and does not separate the placebo and AS group as well as in the serum. Thus, the AS effect on IPL is not as strong as in the serum, although a suggestion of differing lipid profiles by treatment arm was observed. One serum lipid, Glycoproteinacetylsmainlya1acidglycoprotein (GP), did show a clear linear relationship with the PSA level change; however, it was independent of the AS intervention. Baseline SL did not predict high-grade prostate cancer, Ki67 level, or inflammation level in general, according to RFC or LR. AS intervention displays a clear effect on SL level, but only a modest effect on the IPL. Our finding suggests the AS affects the lipids in the prostate as well. GP serum lipid aggregate shows linear relationship with the PSA level change but it is independent of AS intervention. IPL does not correlate with the tumor Gleason grade or Ki-67 proliferation activity. Citation Format: Paavo V. Raittinen, Kati Niemistö, Seppo Auriola, Pauliina Ilmonen, Teemu J. Murtola. Serum and intraprostatic lipidome level shift during statin use among prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3293.