GD2 and GD3 gangliosides as diagnostic biomarkers for all stages and subtypes of epithelial ovarian cancer.

ELISA cancer screening diagnostic test ganglioside immunohistochemistry liquid and tissue biopsy ovarian cancer tumor marker

Journal

Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867

Informations de publication

Date de publication:
2023
Historique:
received: 30 12 2022
accepted: 24 03 2023
medline: 1 5 2023
pubmed: 1 5 2023
entrez: 1 5 2023
Statut: epublish

Résumé

Ovarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for early-stage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers, but they have never before been quantified in OC. We investigated the diagnostic utility of GD2 and GD3 for diagnosis of all subtypes and stages of OC. This retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299) and in two cohorts of serum samples by quantitative ELISA. A discovery cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent model cohort (n=200) was used to train and cross-validate a diagnostic model. GD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A diagnostic model that included serum levels of GD2+GD3+age was superior to the standard of care (CA125, p<0.001) in diagnosing OC and early-stage (I/II) OC. GD2 and GD3 expression was associated with high rates of selectivity and specificity for OC. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early stage. Further research exploring the utility of GD2 and GD3 for diagnosis of OC is warranted.

Sections du résumé

Background UNASSIGNED
Ovarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for early-stage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers, but they have never before been quantified in OC. We investigated the diagnostic utility of GD2 and GD3 for diagnosis of all subtypes and stages of OC.
Methods UNASSIGNED
This retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299) and in two cohorts of serum samples by quantitative ELISA. A discovery cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent model cohort (n=200) was used to train and cross-validate a diagnostic model.
Results UNASSIGNED
GD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A diagnostic model that included serum levels of GD2+GD3+age was superior to the standard of care (CA125, p<0.001) in diagnosing OC and early-stage (I/II) OC.
Conclusion UNASSIGNED
GD2 and GD3 expression was associated with high rates of selectivity and specificity for OC. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early stage. Further research exploring the utility of GD2 and GD3 for diagnosis of OC is warranted.

Identifiants

pubmed: 37124505
doi: 10.3389/fonc.2023.1134763
pmc: PMC10145910
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1134763

Informations de copyright

Copyright © 2023 Galan, Papaluca, Nejatie, Matanes, Brahimi, Tong, Hachim, Yasmeen, Carmona, Klein, Billes, Dawod, Gawande, Jeter, Mes-Masson, Greenwood, Gotlieb and Saragovi.

Déclaration de conflit d'intérêts

Authors HS and WT disclose patent filings protecting claims of intellectual property and the monoclonal antibodies within this report, under License to AOA Dx where authors AJ and PG work and where HS, AD and SB served as consultants. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Obstet Gynecol. 2002 Dec;100(6):1413-6
pubmed: 12468197
Obstet Gynecol. 2022 Feb 1;139(2):157-162
pubmed: 34991145
J Clin Oncol. 2014 Feb 20;32(6):579-86
pubmed: 24449238
Cancer Res. 2012 Aug 1;72(15):3744-52
pubmed: 22649190
PLoS One. 2016 Jun 02;11(6):e0155495
pubmed: 27253331
Int J Mol Sci. 2011 Jan 18;12(1):627-32
pubmed: 21340004
J Biol Chem. 1990 Oct 25;265(30):18242-7
pubmed: 2120225
Biometrics. 1988 Sep;44(3):837-45
pubmed: 3203132
Leukemia. 1994 May;8(5):816-22
pubmed: 8182939
Gynecol Oncol. 2012 Oct;127(1):75-82
pubmed: 22750127
Front Oncol. 2016 Jan 07;5:300
pubmed: 26779443
Cancer Epidemiol Biomarkers Prev. 2016 Sep;25(9):1333-40
pubmed: 27448593
Int J Cancer. 2015 Mar 1;136(5):E359-86
pubmed: 25220842
Oncotarget. 2017 May 9;8(19):31592-31600
pubmed: 28415563
Lancet Oncol. 2020 Aug;21(8):1035-1044
pubmed: 32702311
Heliyon. 2019 Dec 05;5(12):e02826
pubmed: 31867451
Int J Gynecol Cancer. 2021 Feb;31(2):238-244
pubmed: 32540894
Glycoconj J. 2022 Apr;39(2):197-205
pubmed: 35201531
Gynecol Oncol. 2008 Feb;108(2):402-8
pubmed: 18061248
Gynecol Oncol. 2005 Nov;99(2):267-77
pubmed: 16061277
JAMA. 2004 Jun 9;291(22):2705-12
pubmed: 15187051
BJOG. 2004 Jun;111(6):613-8
pubmed: 15198791
Int J Cancer. 1989 Jul 15;44(1):155-60
pubmed: 2744885
Ann Oncol. 2020 Jun;31(6):745-759
pubmed: 33506766
Cancer. 2010 Apr 15;116(8):1918-25
pubmed: 20166213
Obstet Gynecol. 2022 Feb 1;139(2):155-156
pubmed: 34991118
J Immunol. 2018 Dec 15;201(12):3750-3758
pubmed: 30446565
Syst Biol Reprod Med. 2017 Aug;63(4):219-238
pubmed: 28574782
Acta Obstet Gynecol Scand. 2009;88(6):685-92
pubmed: 19455442
Int J Gynecol Cancer. 2017 Oct;27(8):1637-1644
pubmed: 28704327
Maturitas. 1996 Mar;23(2):113-27
pubmed: 8735350
Diagnostics (Basel). 2021 Mar 07;11(3):
pubmed: 33800113
Cancer Res. 1999 Mar 15;59(6):1337-46
pubmed: 10096568
Wiley Interdiscip Rev RNA. 2021 Sep;12(5):e1648
pubmed: 33682310
Mod Pathol. 2006 Jun;19(6):847-53
pubmed: 16607372
Epigenomics. 2014 Jun;6(3):311-27
pubmed: 25111485
Cell Chem Biol. 2019 Jul 18;26(7):1013-1026.e4
pubmed: 31105061
Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1974-8
pubmed: 8127917
Front Immunol. 2020 Sep 29;11:564499
pubmed: 33133075
Blood. 1990 Apr 1;75(7):1564-7
pubmed: 2317562
Am J Obstet Gynecol. 2020 Jan;222(1):56.e1-56.e17
pubmed: 31351062
J Natl Cancer Inst Monogr. 2014 Nov;2014(49):244-54
pubmed: 25417238
Expert Rev Mol Diagn. 2017 Jun;17(6):577-591
pubmed: 28468520
Br J Cancer. 2011 Mar 1;104(5):863-70
pubmed: 21304524
J Gynecol Oncol. 2018 Jan;29(1):e17
pubmed: 29185275

Auteurs

Alba Galan (A)

Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.

Arturo Papaluca (A)

Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.

Ali Nejatie (A)

Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.

Emad Matanes (E)

Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Department of Ob-Gyn, Jewish General Hospital, McGill University and Segal Cancer Center, Lady Davis Institute of Medical Research, Montreal, QC, Canada.

Fouad Brahimi (F)

Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.

Wenyong Tong (W)

Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.

Ibrahim Yaseen Hachim (IY)

Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

Amber Yasmeen (A)

Department of Ob-Gyn, Jewish General Hospital, McGill University and Segal Cancer Center, Lady Davis Institute of Medical Research, Montreal, QC, Canada.

Euridice Carmona (E)

Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montreal, QC, Canada.

Kathleen Oros Klein (KO)

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Université de Montréal, Montreal, QC, Canada.
Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.

Sonja Billes (S)

R&D Department, AOA Dx Inc, Cambridge, MA, United States.

Ahmed E Dawod (AE)

R&D Department, AOA Dx Inc, Cambridge, MA, United States.

Prasad Gawande (P)

R&D Department, AOA Dx Inc, Cambridge, MA, United States.

Anna Milik Jeter (AM)

R&D Department, AOA Dx Inc, Cambridge, MA, United States.

Anne-Marie Mes-Masson (AM)

Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montreal, QC, Canada.
Department of Medicine, Université de Montréal, Montreal, QC, Canada.

Celia M T Greenwood (CMT)

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Université de Montréal, Montreal, QC, Canada.
Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.

Walter H Gotlieb (WH)

Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Department of Ob-Gyn, Jewish General Hospital, McGill University and Segal Cancer Center, Lady Davis Institute of Medical Research, Montreal, QC, Canada.

H Uri Saragovi (HU)

Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
Ophthalmology and Vision Science. McGill University, Montreal, QC, Canada.

Classifications MeSH