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Identification of drug responsible glycogene signature in liver carcinoma from meta-analysis using RNA-seq data

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Abstract

Glycans have attracted much attention in cancer therapeutic strategies, and cell surface proteins and lipids with glycans are known to be altered during the carcinogenic process. However, our understanding of how the glycogenes profile responds to drug stimulation remains incomplete. In this study, we search public databases for Sequence Read Archive data on drug-treated liver cancer cells, with the aim to comprehensively analyze the drug responses of glycogenes via bioinformatic meta-analysis. The study comprised 86 datasets, encompassing eight distinct liver cancer cell lines and 13 different drugs. Differentially expressed genes were quantified, and 399 glycogenes were identified. The glycogenes signature was then analyzed using bioinformatics methodologies. In the Protein-protein interaction network analysis, we identified drug-responsive glycogenes such as Beta-1,4-Galactosyltransferase 1, GDP-Mannose 4,6-Dehydratase, UDP-Glucose Ceramide Glucosyltransferase, and Solute Carrier Family 2 Member 4 as key glycan biomarkers. In the enrichment analysis using the pathway list of glycogenes, the results also demonstrated that drug stimulation resulted in alterations to glycopathway-related genes involved in several processes, namely O-Mannosylation, POMGNT2 Type, Capping, Heparan Sulfate Sulfation, and Glucuronidation pathways. These genes and pathways commonly exhibit variable expression across multiple liver cancer cells in response to the same drug, making them potential targets for new cancer therapies. In addition to their primary roles, drugs may also participate in the regulation of glycans. The insights from this study could pave the way for the development of liver cancer therapies that target the regulation of gene profiles involved in the biosynthesis of glycans.

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Data availability

The data are publicly available in the original repositories. The processed data are available on figshare [19, 21].

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Acknowledgements

I thank for his scientific input in the early phases of the present study.

Author information

Authors and Affiliations

  1. Independent Researcher, Ikawadani-cho, 651-2113, Kobe-shi, Hyogo, Japan

    Tatsuya Koreeda

  2. Honda Biotech. Laboratory, Shimookamoto-cho, 329–1104, Utsunomiya-shi, Tochigi, Japan

    Hiroshi Honda

Authors
  1. Tatsuya Koreeda
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  2. Hiroshi Honda
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Contributions

TK conceived the study, designed the experiments, selected public data sets, downloaded and processed the data, wrote data analysis scripts, interpreted all the data, prepared all figures, and wrote the main manuscript text. HH contributed to the conception and design of the study and provided manuscript review. All authors approved the final version of the manuscript.

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Correspondence to Tatsuya Koreeda.

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Koreeda, T., Honda, H. Identification of drug responsible glycogene signature in liver carcinoma from meta-analysis using RNA-seq data. Glycoconj J 41, 133–149 (2024). https://doi.org/10.1007/s10719-024-10153-y

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  • DOI: https://doi.org/10.1007/s10719-024-10153-y

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