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Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma
Background: Cellular senescence is a typical irreversible form of life stagnation, and recent studies have suggested that long non-coding ribonucleic acids (lncRNA) regulate the occurrence and development of various tumors. In the present study, we attempted to construct a novel signature for predic...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485671/ https://www.ncbi.nlm.nih.gov/pubmed/36147502 http://dx.doi.org/10.3389/fgene.2022.949110 |
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author | Sun, Rui Wang, Xu Chen, Jiajie Teng, Da Chan, Shixin Tu, Xucan Wang, Zhenglin Zuo, Xiaomin Wei, Xiang Lin, Li Zhang, Qing Zhang, Xiaomin Tang, Kechao Zhang, Huabing Chen, Wei |
author_facet | Sun, Rui Wang, Xu Chen, Jiajie Teng, Da Chan, Shixin Tu, Xucan Wang, Zhenglin Zuo, Xiaomin Wei, Xiang Lin, Li Zhang, Qing Zhang, Xiaomin Tang, Kechao Zhang, Huabing Chen, Wei |
author_sort | Sun, Rui |
collection | PubMed |
description | Background: Cellular senescence is a typical irreversible form of life stagnation, and recent studies have suggested that long non-coding ribonucleic acids (lncRNA) regulate the occurrence and development of various tumors. In the present study, we attempted to construct a novel signature for predicting the survival of patients with hepatocellular carcinoma (HCC) and the associated immune landscape based on senescence-related (sr) lncRNAs. Method: Expression profiles of srlncRNAs in 424 patients with HCC were retrieved from The Cancer Genome Atlas database. Lasso and Cox regression analyses were performed to identify differentially expressed lncRNAs related to senescence. The prediction efficiency of the signature was checked using a receiver operating characteristic (ROC) curve, Kaplan–Meier analysis, Cox regression analyses, nomogram, and calibration. The risk groups of the gene set enrichment analysis, immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) were also analyzed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the levels of AC026412.3, AL451069.3, and AL031985.3 in normal hepatic and HCC cell lines. Results: We identified 3 srlncRNAs (AC026412.3, AL451069.3, and AL031985.3) and constructed a new risk model. The results of the ROC curve and Kaplan–Meier analysis suggested that it was concordant with the prediction. Furthermore, a nomogram model was constructed to accurately predict patient prognosis. The risk score also correlated with immune cell infiltration status, immune checkpoint expression, and chemosensitivity. The results of qPCR revealed that AC026412.3 and AL451069.3 were significantly upregulated in hepatoma cell lines. Conclusion: The novel srlncRNA (AC026412.3, AL451069.3, and AL031985.3) signatures may provide insights into new therapies and prognosis predictions for patients with HCC. |
format | Online Article Text |
id | pubmed-9485671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94856712022-09-21 Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma Sun, Rui Wang, Xu Chen, Jiajie Teng, Da Chan, Shixin Tu, Xucan Wang, Zhenglin Zuo, Xiaomin Wei, Xiang Lin, Li Zhang, Qing Zhang, Xiaomin Tang, Kechao Zhang, Huabing Chen, Wei Front Genet Genetics Background: Cellular senescence is a typical irreversible form of life stagnation, and recent studies have suggested that long non-coding ribonucleic acids (lncRNA) regulate the occurrence and development of various tumors. In the present study, we attempted to construct a novel signature for predicting the survival of patients with hepatocellular carcinoma (HCC) and the associated immune landscape based on senescence-related (sr) lncRNAs. Method: Expression profiles of srlncRNAs in 424 patients with HCC were retrieved from The Cancer Genome Atlas database. Lasso and Cox regression analyses were performed to identify differentially expressed lncRNAs related to senescence. The prediction efficiency of the signature was checked using a receiver operating characteristic (ROC) curve, Kaplan–Meier analysis, Cox regression analyses, nomogram, and calibration. The risk groups of the gene set enrichment analysis, immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) were also analyzed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the levels of AC026412.3, AL451069.3, and AL031985.3 in normal hepatic and HCC cell lines. Results: We identified 3 srlncRNAs (AC026412.3, AL451069.3, and AL031985.3) and constructed a new risk model. The results of the ROC curve and Kaplan–Meier analysis suggested that it was concordant with the prediction. Furthermore, a nomogram model was constructed to accurately predict patient prognosis. The risk score also correlated with immune cell infiltration status, immune checkpoint expression, and chemosensitivity. The results of qPCR revealed that AC026412.3 and AL451069.3 were significantly upregulated in hepatoma cell lines. Conclusion: The novel srlncRNA (AC026412.3, AL451069.3, and AL031985.3) signatures may provide insights into new therapies and prognosis predictions for patients with HCC. Frontiers Media S.A. 2022-09-06 /pmc/articles/PMC9485671/ /pubmed/36147502 http://dx.doi.org/10.3389/fgene.2022.949110 Text en Copyright © 2022 Sun, Wang, Chen, Teng, Chan, Tu, Wang, Zuo, Wei, Lin, Zhang, Zhang, Tang, Zhang and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Sun, Rui Wang, Xu Chen, Jiajie Teng, Da Chan, Shixin Tu, Xucan Wang, Zhenglin Zuo, Xiaomin Wei, Xiang Lin, Li Zhang, Qing Zhang, Xiaomin Tang, Kechao Zhang, Huabing Chen, Wei Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma |
title | Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma |
title_full | Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma |
title_fullStr | Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma |
title_full_unstemmed | Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma |
title_short | Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma |
title_sort | development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485671/ https://www.ncbi.nlm.nih.gov/pubmed/36147502 http://dx.doi.org/10.3389/fgene.2022.949110 |
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