Abstract 2447: Identification of tumor marker gangliosides for early cancer detection: A mass spectrometry approach

Abstract

Abstract Tumor-marker gangliosides (TMGs) have enormous potential for early-stage cancer detection as diagnostic biomarkers despite being relatively understudied in this context. AOA Dx is focused on the development of a mass spectrometry platform for the quantitation of TMGs in human serum, particularly disialogangliosides GD2 and GD3. The development of a mass spectrometry platform for TMG quantitation may allow for the identification of diagnostic signatures for early-stage cancer detection. Briefly, we monitored fragment moieties characteristic of gangliosides in an untargeted fashion by mass spectrometry. We then identified those differentially altered in cancerous groups compared to normal, and subsequently performed targeted MRM analysis. Through these investigations, we have identified multiple TMGs, specifically multiple types of GD2 and GD3 species characterized by unique lipid tails across different cancer types in human serum from confirmed cancer diagnoses. Other ganglioside classes including GMs and relatively understudied GTs were also identified in this study. Notably, the serum of melanoma and ovarian cancer patients exhibited significantly increased levels of several ganglioside species compared to age-matched healthy serum, highlighting the potential of TMGs as a promising avenue for cancer diagnosis. Further experiments will focus on refining this mass spectrometry method and expand demographic representation to confirm our initial findings and identify additional TMGs of interest. In addition, we intend to apply immune-based platforms such as thin-layer chromatography and ELISA, which have already shown promising results in the detection and quantitation of these compounds. Taken together, AOA Dx is advancing the development of a high-throughput mass spectrometry platform designed for the detection of TMGs, with a primary focus on GD2 and GD3. Our objective is the identification of a diagnostic disease signature for early-stage cancer detection. The validation of this type of diagnostic panel would allow for expedited diagnosis and treatment of cancers currently diagnosed at late stages, ultimately reducing healthcare costs and increasing survival rates. Future research will aim to validate these biomarkers in independent prospective studies. Citation Format: Rachel Culp-Hill, Collin Hill, Adele Blackler, William Ricketts. Identification of tumor marker gangliosides for early cancer detection: A mass spectrometry approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2447.