Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma
Background: Previous studies have shown that glycosylation of proteins ofen plays an important role in HCC. However, the potential mechanism of glycosylation in HCC has not been described systematically.Methods: We comprehensively evaluated the glycosylation patterns in HCC samples based on 43 glyco...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1001901/full |
| _version_ | 1817975732275511296 |
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| author | Linlin Zhao Linlin Zhao Linlin Zhao Linlin Zhao Linlin Zhao Yang Guo Yang Guo Yang Guo Yang Guo Zhanfeng Liu Jing Ma Yanfeng Peng Dejun Zhang Dejun Zhang |
| author_facet | Linlin Zhao Linlin Zhao Linlin Zhao Linlin Zhao Linlin Zhao Yang Guo Yang Guo Yang Guo Yang Guo Zhanfeng Liu Jing Ma Yanfeng Peng Dejun Zhang Dejun Zhang |
| author_sort | Linlin Zhao |
| collection | DOAJ |
| description | Background: Previous studies have shown that glycosylation of proteins ofen plays an important role in HCC. However, the potential mechanism of glycosylation in HCC has not been described systematically.Methods: We comprehensively evaluated the glycosylation patterns in HCC samples based on 43 glycosylation regulators, and annotated the modification patterns with the enrichment of immune cells and stromal cells. Considering the heterogeneity of HCC patients, the glycosylation score was constructed using single-sample gene set enrichment analysis (ssGSEA). We also explored the drugs that different HCC patients were sensitive to based on glycosylation mode and score.Results: We identified three glycosylation-regulated gene subtypes. By annotating the subtypes, it was found that the glycosylation regulated gene subtypes was highly matched with three immunophenotypes of HCC (immune-inflamed, immune-excluded, and immune-desert), regardless of the characteristics of immune cell infiltration or prognosis. Based on the characteristic genes of glycosylation-regulated gene subtypes, we constructed a glycosylation-related model, and found that glycosylation-related model was highly consistent with the glycosylation regulated gene subtypes. The glycosylation score that evaluates the glycosylation characteristics of a single HCC sample has high prognostic value, and the prognosis of patients with high glycosylation score is significantly worse. Interestingly, we found that the glycosylation score was closely related to tumor node metastasis (TNM) staging. By applying glycosylation-regulated gene subtypes and glycosylation score to explore the sensitivity of different patients to anticancer drugs, it was found that the sensitivity of Thapsigargin, Shikonin, Embelin and Epothilone. B was closely related to the glycosylation mode.Conclusion: This study reveals that the diversity of glycosylation patterns plays an important role in HCC. Therefore, evaluating the glycosylation patterns of patients with HCC will be helpful in identifying the characteristics of immune cell infiltration and selecting accurate treatment methods. |
| first_indexed | 2024-04-13T21:52:56Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T21:52:56Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-9bbcb026826b4f5e8e018ee4c77775952022-12-22T02:28:21ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.10019011001901Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinomaLinlin Zhao0Linlin Zhao1Linlin Zhao2Linlin Zhao3Linlin Zhao4Yang Guo5Yang Guo6Yang Guo7Yang Guo8Zhanfeng Liu9Jing Ma10Yanfeng Peng11Dejun Zhang12Dejun Zhang13Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining, ChinaDepartment of General Surgery, The First People’s Hospital Xining City, Xining, ChinaKey Laboratory of Application and Foundation for High-Altitude Medicine Research in Qinghai Province, Xining, ChinaQinghai-Utah Joint Research Key Laboratory for High Altitude Medicine, Xining, ChinaCollege of Eco-Environmental Engineering, Qinghai University, Xining, ChinaResearch Center for High Altitude Medicine, Medical College of Qinghai University, Xining, ChinaKey Laboratory of Application and Foundation for High-Altitude Medicine Research in Qinghai Province, Xining, ChinaQinghai-Utah Joint Research Key Laboratory for High Altitude Medicine, Xining, ChinaCollege of Eco-Environmental Engineering, Qinghai University, Xining, ChinaDepartment of General Surgery, The First People’s Hospital Xining City, Xining, ChinaCollege of Eco-Environmental Engineering, Qinghai University, Xining, ChinaCollege of Eco-Environmental Engineering, Qinghai University, Xining, ChinaResearch Center for High Altitude Medicine, Medical College of Qinghai University, Xining, ChinaCollege of Eco-Environmental Engineering, Qinghai University, Xining, ChinaBackground: Previous studies have shown that glycosylation of proteins ofen plays an important role in HCC. However, the potential mechanism of glycosylation in HCC has not been described systematically.Methods: We comprehensively evaluated the glycosylation patterns in HCC samples based on 43 glycosylation regulators, and annotated the modification patterns with the enrichment of immune cells and stromal cells. Considering the heterogeneity of HCC patients, the glycosylation score was constructed using single-sample gene set enrichment analysis (ssGSEA). We also explored the drugs that different HCC patients were sensitive to based on glycosylation mode and score.Results: We identified three glycosylation-regulated gene subtypes. By annotating the subtypes, it was found that the glycosylation regulated gene subtypes was highly matched with three immunophenotypes of HCC (immune-inflamed, immune-excluded, and immune-desert), regardless of the characteristics of immune cell infiltration or prognosis. Based on the characteristic genes of glycosylation-regulated gene subtypes, we constructed a glycosylation-related model, and found that glycosylation-related model was highly consistent with the glycosylation regulated gene subtypes. The glycosylation score that evaluates the glycosylation characteristics of a single HCC sample has high prognostic value, and the prognosis of patients with high glycosylation score is significantly worse. Interestingly, we found that the glycosylation score was closely related to tumor node metastasis (TNM) staging. By applying glycosylation-regulated gene subtypes and glycosylation score to explore the sensitivity of different patients to anticancer drugs, it was found that the sensitivity of Thapsigargin, Shikonin, Embelin and Epothilone. B was closely related to the glycosylation mode.Conclusion: This study reveals that the diversity of glycosylation patterns plays an important role in HCC. Therefore, evaluating the glycosylation patterns of patients with HCC will be helpful in identifying the characteristics of immune cell infiltration and selecting accurate treatment methods.https://www.frontiersin.org/articles/10.3389/fgene.2022.1001901/fullhepatocellular carcinomaglycosylationprognosisimmunocyte infiltrationsensitive drugs |
| spellingShingle | Linlin Zhao Linlin Zhao Linlin Zhao Linlin Zhao Linlin Zhao Yang Guo Yang Guo Yang Guo Yang Guo Zhanfeng Liu Jing Ma Yanfeng Peng Dejun Zhang Dejun Zhang Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma Frontiers in Genetics hepatocellular carcinoma glycosylation prognosis immunocyte infiltration sensitive drugs |
| title | Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma |
| title_full | Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma |
| title_fullStr | Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma |
| title_full_unstemmed | Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma |
| title_short | Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma |
| title_sort | characterization of glycosylation regulator mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma |
| topic | hepatocellular carcinoma glycosylation prognosis immunocyte infiltration sensitive drugs |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1001901/full |
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