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

Abstract

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.

Serum Lipidome Profiling Reveals a Distinct Signature of Ovarian Cancer in Korean Women

“…Previous studies have indicated increased gangliosides levels in OC cell lines, tissues, serum, as well as ascites fluid from OC patients 23, 24 , suggesting gangliosides could play a role as OC markers. However, existing data is still sparse regarding the importance of these glycolipids in OC development 23 . A total of twenty-two ganglioside species were detected in serum by LC-MS ( Table S5 ), and their structures confirmed by tandem MS experiments.…”

“…The heterogeneity of OC is one major obstacle in biomarker discovery 23 . HGSC accounts for only 30% of early-stage OC, but 86% of advanced-stage OC.…”

“…A recent study has suggested gangliosides GD2 and GD3 as potential diagnostic OC 23 . Gangliosides are a class of glycolipids present in the plasma membranes of almost all vertebrate cells and are crucial in biological processes that include cell recognition and adhesion, transmembrane signaling, cell growth and differentiation 51 .…”

“…Some studies have suggested the use of lipid panels in combination with CA125 can achieve enhanced diagnostic power 17, 22 . The diagnostic potential of gangliosides, a class of glycolipids involved in immunosuppressive response in tumors, has recently been reported for distinguishing OC patients from non-OC related diseases as well as healthy controls 23 . Increased ganglioside levels in plasma, tissue, and ascites fluid from OC patients have also been reported 23, 24 .…”

“…The diagnostic potential of gangliosides, a class of glycolipids involved in immunosuppressive response in tumors, has recently been reported for distinguishing OC patients from non-OC related diseases as well as healthy controls 23 . Increased ganglioside levels in plasma, tissue, and ascites fluid from OC patients have also been reported 23, 24 . These studies, however, are often hindered by small sample sizes, limited number of early-stage samples, lack of external validation datasets, and inconsistencies in sample collection and processing protocols, thereby limiting the statistical significance and robustness of the final results.…”