Assessment of the diagnostic and prognostic relevance of ACAT1 and CE levels in plasma, peritoneal fluid and tumor tissue of epithelial ovarian cancer patients - a pilot study.
ACAT1
CE
Epithelial ovarian cancer
Ki67
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
10 Apr 2022
10 Apr 2022
Historique:
received:
20
05
2021
accepted:
14
03
2022
entrez:
11
4
2022
pubmed:
12
4
2022
medline:
13
4
2022
Statut:
epublish
Résumé
Abnormal accumulation of acyl-CoA cholesterol acyltransferase-1 (ACAT1) and ACAT1-mediated cholesterol esterified with fatty acids (CE) contribute to cancer progression in various cancers. Our findings of increased CE and ACAT1 levels in epithelial ovarian cancer (EOC) cell lines prompted us to investigate whether such an increase occurs in primary clinical samples obtained from human subjects diagnosed with EOC. We evaluated the diagnostic/prognostic potential of ACAT1 and CE in EOC by: 1) assessing ACAT1 and CE levels in plasma, peritoneal fluid, and ovarian/tumor tissues; 2) assessing diagnostic performance by Receiver Operating Characteristic (ROC) analysis; and 3) comparing expression of ACAT1 and CE with that of tumor proliferation marker, Ki67. ACAT1 protein levels in plasma, peritoneal fluid and tissue were measured via enzyme-linked immunosorbent assay. Tissue expression of ACAT1 and Ki67 proteins were confirmed by immunohistochemistry and mRNA transcript levels were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). CE levels were assessed in plasma, peritoneal fluid (colorimetric assay) and in tissue (thin layer chromatography). Preoperative levels of ACAT1 and CE on the day of surgery were significantly higher in tissue and peritoneal fluid from EOC patients vs. the non-malignant group, which included subjects with benign tumors and normal ovaries; however, no significant differences were observed in plasma. In tissue and peritoneal fluid, positive correlations were observed between CE and ACAT1 levels, as well as between ACAT1/CE and Ki67. ACAT1 and CE accumulation may be linked to the aggressive potential of EOC; therefore, these mediators may be useful biomarkers for EOC prognosis and target-specific treatments.
Sections du résumé
BACKGROUND
BACKGROUND
Abnormal accumulation of acyl-CoA cholesterol acyltransferase-1 (ACAT1) and ACAT1-mediated cholesterol esterified with fatty acids (CE) contribute to cancer progression in various cancers. Our findings of increased CE and ACAT1 levels in epithelial ovarian cancer (EOC) cell lines prompted us to investigate whether such an increase occurs in primary clinical samples obtained from human subjects diagnosed with EOC. We evaluated the diagnostic/prognostic potential of ACAT1 and CE in EOC by: 1) assessing ACAT1 and CE levels in plasma, peritoneal fluid, and ovarian/tumor tissues; 2) assessing diagnostic performance by Receiver Operating Characteristic (ROC) analysis; and 3) comparing expression of ACAT1 and CE with that of tumor proliferation marker, Ki67.
METHODS
METHODS
ACAT1 protein levels in plasma, peritoneal fluid and tissue were measured via enzyme-linked immunosorbent assay. Tissue expression of ACAT1 and Ki67 proteins were confirmed by immunohistochemistry and mRNA transcript levels were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). CE levels were assessed in plasma, peritoneal fluid (colorimetric assay) and in tissue (thin layer chromatography).
RESULTS
RESULTS
Preoperative levels of ACAT1 and CE on the day of surgery were significantly higher in tissue and peritoneal fluid from EOC patients vs. the non-malignant group, which included subjects with benign tumors and normal ovaries; however, no significant differences were observed in plasma. In tissue and peritoneal fluid, positive correlations were observed between CE and ACAT1 levels, as well as between ACAT1/CE and Ki67.
CONCLUSIONS
CONCLUSIONS
ACAT1 and CE accumulation may be linked to the aggressive potential of EOC; therefore, these mediators may be useful biomarkers for EOC prognosis and target-specific treatments.
Identifiants
pubmed: 35399074
doi: 10.1186/s12885-022-09476-6
pii: 10.1186/s12885-022-09476-6
pmc: PMC8994887
doi:
Substances chimiques
Biomarkers, Tumor
0
Fatty Acids
0
Ki-67 Antigen
0
Cholesterol
97C5T2UQ7J
Acyltransferases
EC 2.3.-
ACAT1 protein, human
EC 2.3.1.9
Acetyl-CoA C-Acetyltransferase
EC 2.3.1.9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
387Informations de copyright
© 2022. The Author(s).
Références
Nat Rev Cancer. 2003 Jul;3(7):502-16
pubmed: 12835670
Genes Cancer. 2015 Nov;6(11-12):472-9
pubmed: 26807200
Arterioscler Thromb Vasc Biol. 1998 May;18(5):738-46
pubmed: 9598832
PLoS One. 2017 Jul 18;12(7):e0179558
pubmed: 28719608
J Lipid Res. 2009 Nov;50(11):2203-11
pubmed: 19502590
Med Sci Monit. 2005 Mar;11(3):CR136-42
pubmed: 15735567
Nat Immunol. 2013 Sep;14(9):893-900
pubmed: 23959186
Trends Biochem Sci. 2000 Nov;25(11):530-4
pubmed: 11084360
Cell Prolif. 2011 Aug;44(4):360-71
pubmed: 21645151
Clin Chim Acta. 2005 Sep;359(1-2):27-45
pubmed: 15939411
BMC Cancer. 2018 Aug 24;18(1):850
pubmed: 30143015
Can J Biochem Physiol. 1959 Aug;37(8):911-7
pubmed: 13671378
Breast Cancer Res Treat. 2010 Aug;122(3):661-70
pubmed: 19851860
Int J Gynecol Cancer. 2016 Jan;26(1):43-51
pubmed: 26588231
Nat Rev Cancer. 2003 May;3(5):362-74
pubmed: 12724734
PLoS One. 2020 Jan 9;15(1):e0227707
pubmed: 31917801
Mol Pharmacol. 2010 Nov;78(5):827-36
pubmed: 20702762
Science. 2014 Mar 28;343(6178):1445-6
pubmed: 24675946
Front Pharmacol. 2013 Sep 25;4:119
pubmed: 24093019
Acta Biochim Biophys Sin (Shanghai). 2010 Aug;42(8):568-74
pubmed: 20705598
J Clin Diagn Res. 2017 Feb;11(2):EC08-EC12
pubmed: 28384868
Cell Metab. 2014 Mar 4;19(3):393-406
pubmed: 24606897
Anticancer Res. 2009 Aug;29(8):2875-84
pubmed: 19661290
BMC Cancer. 2015 Jun 09;15:460
pubmed: 26055977
Intern Med Rev (Wash D C). 2017 May;3(5):
pubmed: 29034362
Front Oncol. 2019 Oct 09;9:957
pubmed: 31649873
Am J Physiol Endocrinol Metab. 2009 Jul;297(1):E1-9
pubmed: 19141679
Cancer Biol Ther. 2010 Jun 15;9(12):1025-32
pubmed: 20404512
Oncogene. 2016 Dec 15;35(50):6378-6388
pubmed: 27132508
Nat Commun. 2012;3:1249
pubmed: 23212378
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
Am J Obstet Gynecol. 1990 Jun;162(6):1584-90; discussion 1590-2
pubmed: 2360592
Mol Cell Proteomics. 2014 Dec;13(12):3558-71
pubmed: 25271300
Mol Cancer Res. 2018 Jun;16(6):974-985
pubmed: 29545473
Cancer Res. 2008 Mar 15;68(6):1732-40
pubmed: 18339853
Cancer Sci. 2016 Sep;107(9):1173-8
pubmed: 27297561
J Pathol. 1990 Dec;162(4):295-301
pubmed: 2290114
Am J Obstet Gynecol. 2008 Sep;199(3):215-23
pubmed: 18468571
Cell Motil Cytoskeleton. 2007 Mar;64(3):199-216
pubmed: 17238130
Mol Med Rep. 2016 Dec;14(6):5725-5731
pubmed: 27840988
Curr Oncol Rep. 2006 Nov;8(6):448-54
pubmed: 17040623
EMBO Rep. 2015 Jun;16(6):741-52
pubmed: 25851648
J Ovarian Res. 2013 Aug 30;6(1):60
pubmed: 24001041
Oncogene. 2014 May 22;33(21):2728-36
pubmed: 23770857
N Engl J Med. 2004 Dec 9;351(24):2519-29
pubmed: 15590954
Ann Oncol. 2016 Apr;27 Suppl 1:i63-i65
pubmed: 27141075
Annu Rev Cell Dev Biol. 2006;22:129-57
pubmed: 16753029
J Pharmacol Exp Ther. 2006 Oct;319(1):139-49
pubmed: 16835370
Oncotarget. 2016 Dec 13;7(50):83148-83159
pubmed: 27825119
Gynecol Oncol. 2014 Nov;135(2):333-41
pubmed: 25134999
PLoS One. 2020 Jan 24;15(1):e0228024
pubmed: 31978092
Breast Cancer Res. 2013;15(5):R87
pubmed: 24060386
BMC Cancer. 2018 Dec 10;18(1):1232
pubmed: 30526541
PLoS One. 2018 Feb 28;13(2):e0193318
pubmed: 29489864
PLoS One. 2010 Dec 03;5(12):e14175
pubmed: 21151972