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

Alba Galan; Arturo Papaluca; Arturo Papaluca; Ali Nejatie; Ali Nejatie; Emad Matanes; Emad Matanes; Fouad Brahimi; Wenyong Tong; Wenyong Tong; Ibrahim Yaseen Hachim; Amber Yasmeen; Euridice Carmona; Kathleen Oros Klein; Kathleen Oros Klein; Sonja Billes; Ahmed E. Dawod; Prasad Gawande; Anna Milik Jeter; Anne-Marie Mes-Masson; Anne-Marie Mes-Masson; Celia M. T. Greenwood; Celia M. T. Greenwood; Walter H. Gotlieb; Walter H. Gotlieb; H. Uri Saragovi; H. Uri Saragovi; H. Uri Saragovi

doi:10.3389/fonc.2023.1134763

Frontiers in Oncology (Apr 2023)

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

Alba Galan,
Arturo Papaluca,
Arturo Papaluca,
Ali Nejatie,
Ali Nejatie,
Emad Matanes,
Emad Matanes,
Fouad Brahimi,
Wenyong Tong,
Wenyong Tong,
Ibrahim Yaseen Hachim,
Amber Yasmeen,
Euridice Carmona,
Kathleen Oros Klein,
Kathleen Oros Klein,
Sonja Billes,
Ahmed E. Dawod,
Prasad Gawande,
Anna Milik Jeter,
Anne-Marie Mes-Masson,
Anne-Marie Mes-Masson,
Celia M. T. Greenwood,
Celia M. T. Greenwood,
Walter H. Gotlieb,
Walter H. Gotlieb,
H. Uri Saragovi,
H. Uri Saragovi,
H. Uri Saragovi

Affiliations

Alba Galan: Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada
Arturo Papaluca: Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada
Arturo Papaluca: Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Ali Nejatie: Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada
Ali Nejatie: Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Emad Matanes: Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada
Emad Matanes: Department of Ob-Gyn, Jewish General Hospital, McGill University and Segal Cancer Center, Lady Davis Institute of Medical Research, Montreal, QC, Canada
Fouad Brahimi: Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada
Wenyong Tong: Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada
Wenyong Tong: Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Ibrahim Yaseen Hachim: Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Amber Yasmeen: Department of Ob-Gyn, Jewish General Hospital, McGill University and Segal Cancer Center, Lady Davis Institute of Medical Research, Montreal, QC, Canada
Euridice Carmona: Centre de recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montreal, QC, Canada
Kathleen Oros Klein: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Université de Montréal, Montreal, QC, Canada
Kathleen Oros Klein: Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada
Sonja Billes: R&D Department, AOA Dx Inc, Cambridge, MA, United States
Ahmed E. Dawod: R&D Department, AOA Dx Inc, Cambridge, MA, United States
Prasad Gawande: R&D Department, AOA Dx Inc, Cambridge, MA, United States
Anna Milik Jeter: R&D Department, AOA Dx Inc, Cambridge, MA, United States
Anne-Marie Mes-Masson: Centre de recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montreal, QC, Canada
Anne-Marie Mes-Masson: Department of Medicine, Université de Montréal, Montreal, QC, Canada
Celia M. T. Greenwood: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Université de Montréal, Montreal, QC, Canada
Celia M. T. Greenwood: 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: Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada
Walter H. Gotlieb: 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: Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada
H. Uri Saragovi: Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
H. Uri Saragovi: 0Ophthalmology and Vision Science. McGill University, Montreal, QC, Canada

DOI: https://doi.org/10.3389/fonc.2023.1134763
Journal volume & issue: Vol. 13

Abstract

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BackgroundOvarian 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.MethodsThis 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.ResultsGD2 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.ConclusionGD2 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.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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