Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
Clinic for General Surgery, Military Medical Academy, 17 Crnotravska St, 11000 Belgrade, Serbia.
Biochem Pharmacol. 2022 Feb;196:114595. doi: 10.1016/j.bcp.2021.114595. Epub 2021 May 6.
Colorectal cancer (CRC) is a highly prevalent malignancy. Previous studies suggested that cholesterol might play a signficant role in malignant transformation and proliferation. Non-cholesterol sterols (NCS), which are transported by serum lipoproteins alongside cholesterol, are regarded as cholesterol synthesis and absorption markers. Quantification of NCS in serum and HDL fraction (NCS), could provide a better insight into the cholesterol metabolism. The aim of this study was to examine the status of cholesterol synthesis and cholesterol absorption markers in serum and HDL fraction and explore their interrelation in CRC patients. Current study was designed as observational, case-control study. The study included 73 CRC patients and 95 healthy subjects. NCS and NCS concentrations were determined by HPLC-MS/MS. Based on NCS and NCS concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P<0.001) and NCS concentrations (P<0.001 for desmosterol; P<0.05 for lathosterol, P=0.001 for campesterol, P<0.001 for β-sitosterol). NCS/NCS (P<0.005 for desmosterol/desmosterol; P<0.05 for lathosterol/lathosterol; P<0.001 for both β-sitosterol/β-sitosterol and campesterol/campesterol) and synthesis to absorption ratio (CSI/CAI) (P<0.005) were increased in CRC patients. Additionally, low serum concentrations of desmosterol (P<0.001; OR=0.329; 95%CI (0.199-0.542)) and campesterol (P<0.001; OR=0.540; 95%CI (0.424-0.687)) were independent predictors of CRC presence. Our data suggest that cholesterol homeostasis in CRC is shifted towards increased synthesis. Relative abundance of NCS in HDL particles is increased, suggesting the possible overproduction of cholesterol precursors in peripheral tissues.
结直肠癌（CRC）是一种高发的恶性肿瘤。先前的研究表明，胆固醇可能在恶性转化和增殖中发挥重要作用。非胆固醇甾醇（NCS）与胆固醇一起由血清脂蛋白转运，被认为是胆固醇合成和吸收的标志物。定量检测血清和高密度脂蛋白（HDL）部分中的 NCS（NCS）可以更好地了解胆固醇代谢。本研究旨在检查 CRC 患者血清和 HDL 部分中胆固醇合成和胆固醇吸收标志物的状态，并探讨它们之间的相互关系。本研究设计为观察性病例对照研究。研究包括 73 例 CRC 患者和 95 例健康对照者。采用高效液相色谱-串联质谱法（HPLC-MS/MS）测定 NCS 和 NCS 浓度。基于 NCS 和 NCS 浓度，计算了不同的胆固醇稳态指数。患者的 NCS（P<0.001）和 NCS 浓度（desmosterol 为 P<0.001；lathosterol 为 P<0.05；campesterol 为 P=0.001；β-谷固醇为 P<0.001）显著降低。NCS/NCS（desmosterol/desmosterol 为 P<0.005；lathosterol/lathosterol 为 P<0.05；β-谷固醇/β-谷固醇和 campesterol/campesterol 均为 P<0.001）和合成吸收比（CSI/CAI）（P<0.005）在 CRC 患者中增加。此外，血清中 desmosterol（P<0.001；OR=0.329；95%CI（0.199-0.542））和 campesterol（P<0.001；OR=0.540；95%CI（0.424-0.687））浓度低是 CRC 存在的独立预测因子。我们的数据表明，CRC 中的胆固醇稳态向合成增加转变。HDL 颗粒中 NCS 的相对丰度增加，表明外周组织中胆固醇前体可能过度产生。
