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Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma

BACKGROUND: Cellular senescence is a tumor suppressive response in which the cell cycle is in a state of permanent arrest and can inhibit tumor cell proliferation. In recent years, induction of cellular senescence has been shown to be important for antitumor therapy, and the link between cellular se...

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Autores principales: Sun, Liang, Liu, Zitao, Ning, Ke, Wu, Zhipeng, Chen, Zhendong, Wu, Zhengyi, Yin, Xiangbao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761989/
https://www.ncbi.nlm.nih.gov/pubmed/36536279
http://dx.doi.org/10.1186/s12575-022-00187-7
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author Sun, Liang
Liu, Zitao
Ning, Ke
Wu, Zhipeng
Chen, Zhendong
Wu, Zhengyi
Yin, Xiangbao
author_facet Sun, Liang
Liu, Zitao
Ning, Ke
Wu, Zhipeng
Chen, Zhendong
Wu, Zhengyi
Yin, Xiangbao
author_sort Sun, Liang
collection PubMed
description BACKGROUND: Cellular senescence is a tumor suppressive response in which the cell cycle is in a state of permanent arrest and can inhibit tumor cell proliferation. In recent years, induction of cellular senescence has been shown to be important for antitumor therapy, and the link between cellular senescence and clinical prognosis and immunotherapy of hepatocellular carcinoma is still unknown. METHODS: We performed enrichment analysis of genes in three cellular senescence gene sets, screened for gene sets significantly enriched in hepatocellular carcinoma and extracted genes from them. Signature were constructed using senescence-related genes, and their expression was verified at the protein and RNA levels. Survival, clinical staging and grading, immune infiltration, immunotherapy, and drug sensitivity were also analyzed between risk groups. RESULTS: The q-PCR and immunohistochemistry results revealed significant differences in the expression of the signature genes between normal and tumor tissues. Significant differences in clinicopathological features, prognosis and immune infiltration were observed between risk groups. In the low-risk group, better OS and lower TMB scores were demonstrated, while the high-risk group had higher immune checkpoint expression, as well as lower risk of immune escape. In addition, we found that the High-risk group was more sensitive to sorafenib. CONCLUSION: In summary, the signature constructed using aging-related genes can reliably predict patient prognosis and immunotherapy efficacy, providing a new idea for immune system therapy of hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12575-022-00187-7.
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spelling pubmed-97619892022-12-20 Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma Sun, Liang Liu, Zitao Ning, Ke Wu, Zhipeng Chen, Zhendong Wu, Zhengyi Yin, Xiangbao Biol Proced Online Research BACKGROUND: Cellular senescence is a tumor suppressive response in which the cell cycle is in a state of permanent arrest and can inhibit tumor cell proliferation. In recent years, induction of cellular senescence has been shown to be important for antitumor therapy, and the link between cellular senescence and clinical prognosis and immunotherapy of hepatocellular carcinoma is still unknown. METHODS: We performed enrichment analysis of genes in three cellular senescence gene sets, screened for gene sets significantly enriched in hepatocellular carcinoma and extracted genes from them. Signature were constructed using senescence-related genes, and their expression was verified at the protein and RNA levels. Survival, clinical staging and grading, immune infiltration, immunotherapy, and drug sensitivity were also analyzed between risk groups. RESULTS: The q-PCR and immunohistochemistry results revealed significant differences in the expression of the signature genes between normal and tumor tissues. Significant differences in clinicopathological features, prognosis and immune infiltration were observed between risk groups. In the low-risk group, better OS and lower TMB scores were demonstrated, while the high-risk group had higher immune checkpoint expression, as well as lower risk of immune escape. In addition, we found that the High-risk group was more sensitive to sorafenib. CONCLUSION: In summary, the signature constructed using aging-related genes can reliably predict patient prognosis and immunotherapy efficacy, providing a new idea for immune system therapy of hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12575-022-00187-7. BioMed Central 2022-12-19 /pmc/articles/PMC9761989/ /pubmed/36536279 http://dx.doi.org/10.1186/s12575-022-00187-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sun, Liang
Liu, Zitao
Ning, Ke
Wu, Zhipeng
Chen, Zhendong
Wu, Zhengyi
Yin, Xiangbao
Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma
title Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma
title_full Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma
title_fullStr Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma
title_full_unstemmed Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma
title_short Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma
title_sort comprehensive analysis of cellular senescence-related genes in prognosis, molecular characterization and immunotherapy of hepatocellular carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761989/
https://www.ncbi.nlm.nih.gov/pubmed/36536279
http://dx.doi.org/10.1186/s12575-022-00187-7
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