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Open AccessArticle

RNA Sequencing-Based Identification of Ganglioside GD2-Positive Cancer Phenotype

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho- Maklaya St., 117997 Moscow, Russia
2
Sechenov First Moscow State Medical University, 8-2, Trubetskaya St., 119992 Moscow, Russia
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Omicsway Corp., 340 S Lemon Ave, 6040, Walnut, CA 91789, USA
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Orekhovich Institute of Biomedical Chemistry, 10, Pogodinskaya St., 119121 Moscow, Russia
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D. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, 1, Samory Mashela St., 117997 Moscow, Russia
6
Real Target LLC, 108841 Moscow, Russia
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Skolkovo Institute of Science and Technology, 3, Nobelya St., 121205 Moscow, Russia
8
Moscow Institute of Physics and Technology (National Research University), 141700 Moscow, Russia
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Oncobox ltd., 121205 Moscow, Russia
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(6), 142; https://doi.org/10.3390/biomedicines8060142
Received: 27 April 2020 / Revised: 20 May 2020 / Accepted: 27 May 2020 / Published: 30 May 2020
(This article belongs to the Section Cancer Therapeutics)
The tumor-associated ganglioside GD2 represents an attractive target for cancer immunotherapy. GD2-positive tumors are more responsive to such targeted therapy, and new methods are needed for the screening of GD2 molecular tumor phenotypes. In this work, we built a gene expression-based binary classifier predicting the GD2-positive tumor phenotypes. To this end, we compared RNA sequencing data from human tumor biopsy material from experimental samples and public databases as well as from GD2-positive and GD2-negative cancer cell lines, for expression levels of genes encoding enzymes involved in ganglioside biosynthesis. We identified a 2-gene expression signature combining ganglioside synthase genes ST8SIA1 and B4GALNT1 that serves as a more efficient predictor of GD2-positive phenotype (Matthews Correlation Coefficient (MCC) 0.32, 0.88, and 0.98 in three independent comparisons) compared to the individual ganglioside biosynthesis genes (MCC 0.02–0.32, 0.1–0.75, and 0.04–1 for the same independent comparisons). No individual gene showed a higher MCC score than the expression signature MCC score in two or more comparisons. Our diagnostic approach can hopefully be applied for pan-cancer prediction of GD2 phenotypes using gene expression data. View Full-Text
Keywords: ganglioside GD2; GD2-positive tumors; neuroblastoma; glioma; immunotherapy; molecular diagnostics; NGS; ganglioside biosynthesis; targeted therapy; RNA sequencing ganglioside GD2; GD2-positive tumors; neuroblastoma; glioma; immunotherapy; molecular diagnostics; NGS; ganglioside biosynthesis; targeted therapy; RNA sequencing
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Sorokin, M.; Kholodenko, I.; Kalinovsky, D.; Shamanskaya, T.; Doronin, I.; Konovalov, D.; Mironov, A.; Kuzmin, D.; Nikitin, D.; Deyev, S.; Buzdin, A.; Kholodenko, R. RNA Sequencing-Based Identification of Ganglioside GD2-Positive Cancer Phenotype. Biomedicines 2020, 8, 142.

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