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

Authorized Users Only
2022
Authors
Vladimirov, Sandra
Gojković, Tamara
Zeljković, Aleksandra
Jelić-Ivanović, Zorana
Zeljković, Dejan
Antonić, Tamara
Trifunović, Bratislav
Spasojević-Kalimanovska, Vesna
Article (Published version)
Metadata
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Abstract
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 (NCSHDL), 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 NCSHDL concentrations were determined by HPLC-MS/MS. Based on NCS and NCSHDL concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P<0.001) and NCSHDL concentrations... (P<0.001 for desmosterolHDL; P<0.05 for lathosterolHDL, P=0.001 for campesterolHDL, P<0.001 for β-sitosterolHDL). NCSHDL/NCS (P<0.005 for desmosterolHDL/desmosterol; P<0.05 for lathosterolHDL/lathosterol; P<0.001 for both β-sitosterolHDL/β-sitosterol and campesterolHDL/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.

Keywords:
Dyslipidemia / Colorectal cancer / Cholesterol synthesis and absorption / HDL / Non-cholesterol sterols / Peripheral tissue
Source:
Biochemical Pharmacology, 2022, 196
Publisher:
  • Elsevier Inc.
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)

DOI: 10.1016/j.bcp.2021.114595

ISSN: 0006-2952

WoS: 000772634800002

Scopus: 2-s2.0-85105603646
[ Google Scholar ]
5
3
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/4178
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Vladimirov, Sandra
AU  - Gojković, Tamara
AU  - Zeljković, Aleksandra
AU  - Jelić-Ivanović, Zorana
AU  - Zeljković, Dejan
AU  - Antonić, Tamara
AU  - Trifunović, Bratislav
AU  - Spasojević-Kalimanovska, Vesna
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4178
AB  - 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 (NCSHDL), 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 NCSHDL concentrations were determined by HPLC-MS/MS. Based on NCS and NCSHDL concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P<0.001) and NCSHDL concentrations (P<0.001 for desmosterolHDL; P<0.05 for lathosterolHDL, P=0.001 for campesterolHDL, P<0.001 for β-sitosterolHDL). NCSHDL/NCS (P<0.005 for desmosterolHDL/desmosterol; P<0.05 for lathosterolHDL/lathosterol; P<0.001 for both β-sitosterolHDL/β-sitosterol and campesterolHDL/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.
PB  - Elsevier Inc.
T2  - Biochemical Pharmacology
T1  - Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?
VL  - 196
DO  - 10.1016/j.bcp.2021.114595
ER  - 
@article{
author = "Vladimirov, Sandra and Gojković, Tamara and Zeljković, Aleksandra and Jelić-Ivanović, Zorana and Zeljković, Dejan and Antonić, Tamara and Trifunović, Bratislav and Spasojević-Kalimanovska, Vesna",
year = "2022",
abstract = "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 (NCSHDL), 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 NCSHDL concentrations were determined by HPLC-MS/MS. Based on NCS and NCSHDL concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P<0.001) and NCSHDL concentrations (P<0.001 for desmosterolHDL; P<0.05 for lathosterolHDL, P=0.001 for campesterolHDL, P<0.001 for β-sitosterolHDL). NCSHDL/NCS (P<0.005 for desmosterolHDL/desmosterol; P<0.05 for lathosterolHDL/lathosterol; P<0.001 for both β-sitosterolHDL/β-sitosterol and campesterolHDL/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.",
publisher = "Elsevier Inc.",
journal = "Biochemical Pharmacology",
title = "Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?",
volume = "196",
doi = "10.1016/j.bcp.2021.114595"
}
Vladimirov, S., Gojković, T., Zeljković, A., Jelić-Ivanović, Z., Zeljković, D., Antonić, T., Trifunović, B.,& Spasojević-Kalimanovska, V.. (2022). Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?. in Biochemical Pharmacology
Elsevier Inc.., 196.
https://doi.org/10.1016/j.bcp.2021.114595
Vladimirov S, Gojković T, Zeljković A, Jelić-Ivanović Z, Zeljković D, Antonić T, Trifunović B, Spasojević-Kalimanovska V. Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?. in Biochemical Pharmacology. 2022;196.
doi:10.1016/j.bcp.2021.114595 .
Vladimirov, Sandra, Gojković, Tamara, Zeljković, Aleksandra, Jelić-Ivanović, Zorana, Zeljković, Dejan, Antonić, Tamara, Trifunović, Bratislav, Spasojević-Kalimanovska, Vesna, "Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?" in Biochemical Pharmacology, 196 (2022),
https://doi.org/10.1016/j.bcp.2021.114595 . .

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