Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?

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_HDL), 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_HDL concentrations were determined by HPLC-MS/MS. Based on NCS and NCS_HDL concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P<0.001) and NCS_HDL concentrations (P<0.001 for desmosterol_HDL; P<0.05 for lathosterol_HDL, P=0.001 for campesterol_HDL, P<0.001 for β-sitosterol_HDL). NCS_HDL/NCS (P<0.005 for desmosterol_HDL/desmosterol; P<0.05 for lathosterol_HDL/lathosterol; P<0.001 for both β-sitosterol_HDL/β-sitosterol and campesterol_HDL/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.