Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma

Paret, Claudia; Wingerter, Arthur; Seidmann, Larissa; Ustjanzew, Arsenij; Sathyamurthy, Shobha; Ludwig, Jannis; Schwickerath, Philipp; Brignole, Chiara; Pastorino, Fabio; Wagner, Saskia; El Malki, Khalifa; Roth, Wilfried; Sandhoff, Roger; Faber, Jörg

doi:10.3390/ijms26178431

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Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma

by

Claudia Paret

^1,2,3,4,†

,

Arthur Wingerter

^1,†

,

Larissa Seidmann

⁵,

Arsenij Ustjanzew

⁶

,

Shobha Sathyamurthy

⁷,

Jannis Ludwig

⁷,

Philipp Schwickerath

⁷,

Chiara Brignole

⁸

,

Fabio Pastorino

⁸

,

Saskia Wagner

¹

,

Khalifa El Malki

¹,

Wilfried Roth

⁵,

Roger Sandhoff

^7,‡ and

Jörg Faber

^{1,2,3,4,*,‡}

¹

Department of Pediatric Hematology/Oncology, Center for Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany

²

Helmholtz-Institute for Translational Oncology Mainz (HI-TRON), 55131 Mainz, Germany

³

University Cancer Center (UCT), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany

⁴

German Cancer Consortium (DKTK), Site Frankfurt/Mainz, Germany, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

⁵

Institute of Pathology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany

⁶

Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany

⁷

Lipid Pathobiochemistry, German Cancer Research Center, 69120 Heidelberg, Germany

⁸

Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genoa, Italy

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to the work.

^‡

Shared last authorship.

Int. J. Mol. Sci. 2025, 26(17), 8431; https://doi.org/10.3390/ijms26178431

Submission received: 1 August 2025 / Revised: 21 August 2025 / Accepted: 27 August 2025 / Published: 29 August 2025

(This article belongs to the Special Issue Neuroblastoma: Molecular Pathology, Diagnostics and Therapeutics)

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Abstract

High-risk (HR) neuroblastoma (NBL) patients often receive standardized treatment despite wide variations in clinical outcomes, underscoring the need for improved stratification tools. A distinguishing feature of NBL is the patient-specific expression of gangliosides (GGs), particularly GD2, which may serve as biomarkers. We analyzed GG profiles in 18 patient-derived tumors and 11 NBL cell lines using thin-layer chromatography and mass spectrometry. Expression of 0-, a-, and b-series GGs was examined and correlated with clinical risk, outcome, and gene expression data. Low-risk (LR) tumors expressed higher levels of complex b-series GGs. In HR tumors, five GG profiles (A–E) were identified. Profile A featured complex b-series GGs; B showed GD2 dominance; C showed synthesis arrest at GM3 or GD3 due to low expression of the GM2/GD2 synthase, encoded by the B4GALNT1 gene; D included complex a- and b-series GGs; and E was marked by GM2 and GD1a prevalence. B4GALNT1 expression served as a prognostic marker. Relapsed tumors following anti-GD2 therapy typically exhibited reduced GD2 levels, except for one profile A tumor that displayed a ceramide anchor shorter than those found in LR tumors. Astonishingly, the ceramide anchor composition of GD2 itself appears to separate LR and HR NBL, hinting at a role of ceramide synthases in NBL biology. All cell lines expressed GM2, but exhibited very low levels of complex b-series GGs. Profile C was found only in cell lines of the mesenchymal subtype. These findings support further investigation of GG composition and associated enzyme expression as potential biomarkers for risk stratification and treatment response in NBL.

Keywords: neuroblastoma; GD2; gangliosides; B4GALNT1; dinutuximab; naxitamab; ceramide

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MDPI and ACS Style

Paret, C.; Wingerter, A.; Seidmann, L.; Ustjanzew, A.; Sathyamurthy, S.; Ludwig, J.; Schwickerath, P.; Brignole, C.; Pastorino, F.; Wagner, S.; et al. Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma. Int. J. Mol. Sci. 2025, 26, 8431. https://doi.org/10.3390/ijms26178431

AMA Style

Paret C, Wingerter A, Seidmann L, Ustjanzew A, Sathyamurthy S, Ludwig J, Schwickerath P, Brignole C, Pastorino F, Wagner S, et al. Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma. International Journal of Molecular Sciences. 2025; 26(17):8431. https://doi.org/10.3390/ijms26178431

Chicago/Turabian Style

Paret, Claudia, Arthur Wingerter, Larissa Seidmann, Arsenij Ustjanzew, Shobha Sathyamurthy, Jannis Ludwig, Philipp Schwickerath, Chiara Brignole, Fabio Pastorino, Saskia Wagner, and et al. 2025. "Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma" International Journal of Molecular Sciences 26, no. 17: 8431. https://doi.org/10.3390/ijms26178431

APA Style

Paret, C., Wingerter, A., Seidmann, L., Ustjanzew, A., Sathyamurthy, S., Ludwig, J., Schwickerath, P., Brignole, C., Pastorino, F., Wagner, S., El Malki, K., Roth, W., Sandhoff, R., & Faber, J. (2025). Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma. International Journal of Molecular Sciences, 26(17), 8431. https://doi.org/10.3390/ijms26178431

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Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma

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