The impact of cholesterol and its metabolites on the ovarian tumor microenvironment and cancer progression
type: CreativeWork
description: There is an urgent need to develop new therapeutic or lifestyle strategies for treating ovarian cancer due to its high recurrence and mortality rate. In this regard, we and others have found that cholesterol appears to be clinically important for ovarian cancer survival, highlighting it and its metabolism as potential therapeutic targets for improving the lifespan of patients. In a cohort of 153 patients, we found high total, LDL or non-HDL cholesterol was associated with high tumor grade, which in turn was associated with increased likelihood of cancer spreading to secondary locations. Consistently, high HDL-C was protective as it was associated with early stage cancers and better progression-free survival (PFS). Patients prescribed cholesterol lowering drugs such as statins, cholesterol absorption inhibitors or fiber were associated with significantly improved overall survival (OS). In addition, prescriptions at least one year prior to diagnosis was associated with increased probability of low tumor grades. Cytochrome P450 enzymes catalyze the first steps in cholesterol metabolism pathways. Among them, CYP27A1 is highly expressed in myeloid cells and oxidizes cholesterol into 27-hydroxychoelsterol (27HC), which is the most abundant oxysterol and an endogenous signaling molecule. In addition, serum 27HC concentration closely correlates to that of cholesterol. Analysis of publicly available databases indicated that low tumoral CYP27A1 expression was associated with better progression-free survival and overall survival. Conversely, high tumoral CYP7B1 expression, the enzyme that metabolites 27HC, was associated with improved progression-free survival. Therefore, we hypothesized that CYP27A1/27HC might be mediating the effects of cholesterol on cancer survival. CYP27A1 deletion or exogenous 27HC had no effects on cancer cellular proliferation, however, we found ovarian tumors failed to grow in CYP27A1-/- mice, eventually completely regressing, while treatment with exo…
abstract: There is an urgent need to develop new therapeutic or lifestyle strategies for treating ovarian cancer due to its high recurrence and mortality rate. In this regard, we and others have found that cholesterol appears to be clinically important for ovarian cancer survival, highlighting it and its metabolism as potential therapeutic targets for improving the lifespan of patients. In a cohort of 153 patients, we found high total, LDL or non-HDL cholesterol was associated with high tumor grade, which in turn was associated with increased likelihood of cancer spreading to secondary locations. Consistently, high HDL-C was protective as it was associated with early stage cancers and better progression-free survival (PFS). Patients prescribed cholesterol lowering drugs such as statins, cholesterol absorption inhibitors or fiber were associated with significantly improved overall survival (OS). In addition, prescriptions at least one year prior to diagnosis was associated with increased probability of low tumor grades. Cytochrome P450 enzymes catalyze the first steps in cholesterol metabolism pathways. Among them, CYP27A1 is highly expressed in myeloid cells and oxidizes cholesterol into 27-hydroxychoelsterol (27HC), which is the most abundant oxysterol and an endogenous signaling molecule. In addition, serum 27HC concentration closely correlates to that of cholesterol. Analysis of publicly available databases indicated that low tumoral CYP27A1 expression was associated with better progression-free survival and overall survival. Conversely, high tumoral CYP7B1 expression, the enzyme that metabolites 27HC, was associated with improved progression-free survival. Therefore, we hypothesized that CYP27A1/27HC might be mediating the effects of cholesterol on cancer survival. CYP27A1 deletion or exogenous 27HC had no effects on cancer cellular proliferation, however, we found ovarian tumors failed to grow in CYP27A1-/- mice, eventually completely regressing, while treatment with exo…
author: He, Sisi
language: en
keywords: cholesterol, CYP27A1
date published: 2020-08-27T00:49:56Z
date modified: 2026-07-22T22:24:48Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/108251