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

Autor:	Galan A; Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada., Papaluca A; Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.; Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada., Nejatie A; Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.; Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada., 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., Brahimi F; Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada., Tong W; Translational Cancer Center, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada.; Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada., Hachim IY; Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates., Yasmeen A; Department of Ob-Gyn, Jewish General Hospital, McGill University and Segal Cancer Center, Lady Davis Institute of Medical Research, Montreal, QC, Canada., Carmona E; Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montreal, QC, Canada., 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., Billes S; R&D Department, AOA Dx Inc, Cambridge, MA, United States., Dawod AE; R&D Department, AOA Dx Inc, Cambridge, MA, United States., Gawande P; R&D Department, AOA Dx Inc, Cambridge, MA, United States., Jeter AM; R&D Department, AOA Dx Inc, Cambridge, MA, United States., 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., 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., 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., 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.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2023 Apr 14; Vol. 13, pp. 1134763. Date of Electronic Publication: 2023 Apr 14 (Print Publication: 2023).
DOI:	10.3389/fonc.2023.1134763
Abstrakt:	Background: 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: 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: 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: 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. Competing Interests: 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. (Copyright © 2023 Galan, Papaluca, Nejatie, Matanes, Brahimi, Tong, Hachim, Yasmeen, Carmona, Klein, Billes, Dawod, Gawande, Jeter, Mes-Masson, Greenwood, Gotlieb and Saragovi.)
Databáze:	MEDLINE
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