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A Novel HCC Prognosis Predictor EEF1E1 Is Related to Immune Infiltration and May Be Involved in EEF1E1/ATM/p53 Signaling
BACKGROUND: EEF1E1 has been reported to play a role in ovarian cancer, breast cancer, non-small cell lung cancer and other cancers, but its role and mechanism in hepatocellular carcinoma (HCC) are still unknown. METHODS: EEF1E1 expression in human HCC was analyzed via the GTEx and TCGA database. Log...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285289/ https://www.ncbi.nlm.nih.gov/pubmed/34282404 http://dx.doi.org/10.3389/fonc.2021.700972 |
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author | Han, Ruiqin Feng, Penghui Pang, Junyi Zou, Dingfeng Li, Xiaolu Geng, Chao Li, Lili Min, Jie Shi, Jing |
author_facet | Han, Ruiqin Feng, Penghui Pang, Junyi Zou, Dingfeng Li, Xiaolu Geng, Chao Li, Lili Min, Jie Shi, Jing |
author_sort | Han, Ruiqin |
collection | PubMed |
description | BACKGROUND: EEF1E1 has been reported to play a role in ovarian cancer, breast cancer, non-small cell lung cancer and other cancers, but its role and mechanism in hepatocellular carcinoma (HCC) are still unknown. METHODS: EEF1E1 expression in human HCC was analyzed via the GTEx and TCGA database. Logistic regression analysis was used to analyze the clinicopathological correlation of EEF1E1 expression. The correlation between EEF1E1 expression and patients’ prognosis was analyzed in HCC, shown by forest plots, nomogram and Kaplan–Meier curves. Hazard ratio (HR) with 95% confidence intervals and log-rank p-value were calculated via multivariate/univariate survival analyses. Moreover, the correlation between EEF1E1 and tumor immune infiltration was analyzed using the gsva package with the ssgsea algorithm. Pearson correlation was used to investigate the correlation between EEF1E1 expression and p53 pathway genes expression. Two third-party databases were used to validate the content of EEF1E1 protein and mRNA expression patterns and prognosis analysis. The immunohistochemistry and multiplex immunohistochemistry was used to verify the bio-informatics results. RESULTS: EEF1E1 mRNA and protein expression in tumor was statistically higher than normal (EEF1E1 mRNA: p < 0.001; EEF1E1 protein: p < 0.01). Results from paired t-test (cancer and adjacent tissues) exhibited consistent trend (t = 7.572, p < 0.001). Immunohistochemistry showed that EEF1E1 is highly expressed in cancer. The expression of EEF1E1 was positively correlated with body weight, BMI, tumor status, vascular invasion, AFP, logistic grade, T stage and pathological stage. The univariate Cox model revealed that high EEF1E1 expression was strongly associated with worse OS (HR=2.581; 95% CI: 1.782-3.739; p < 0.001), as was T stage, pathologic stage, Histologic grade. High EEF1E1 expression was the only independent prognostic factor associated with OS (HR=2.57; 95% CI: 1.715-3.851; p < 0.001) in the multivariate analysis. EEF1E1 was significantly correlated with various immune cells, including cytotoxic cells, DC, macrophages, neutrophils, NK cd56bright, TFH, Tgd, Th17, Th2, Treg. Multiplex immunohistochemistry showed that the EEF1E1 protein level is positively correlated to the CD3, CD4, PD1 and is negatively correlated to the CD8. The expression level of EEF1E1 in HCC was significantly correlated with the key genes involved in the p53 pathway. The expression of EEF1E1, ATM, p53 and CASPASE3 in HCC tissues was significantly higher than that in adjacent tissues. CONCLUSION: EEF1E1 is highly expressed in cancer tissues in HCC. EEF1E1’s high expression is significantly correlated with worse prognosis and immune cell infiltration of HCC. EEF1E1 may be participating in EEF1E1/ATM/p53 signaling pathway in HCC. |
format | Online Article Text |
id | pubmed-8285289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82852892021-07-18 A Novel HCC Prognosis Predictor EEF1E1 Is Related to Immune Infiltration and May Be Involved in EEF1E1/ATM/p53 Signaling Han, Ruiqin Feng, Penghui Pang, Junyi Zou, Dingfeng Li, Xiaolu Geng, Chao Li, Lili Min, Jie Shi, Jing Front Oncol Oncology BACKGROUND: EEF1E1 has been reported to play a role in ovarian cancer, breast cancer, non-small cell lung cancer and other cancers, but its role and mechanism in hepatocellular carcinoma (HCC) are still unknown. METHODS: EEF1E1 expression in human HCC was analyzed via the GTEx and TCGA database. Logistic regression analysis was used to analyze the clinicopathological correlation of EEF1E1 expression. The correlation between EEF1E1 expression and patients’ prognosis was analyzed in HCC, shown by forest plots, nomogram and Kaplan–Meier curves. Hazard ratio (HR) with 95% confidence intervals and log-rank p-value were calculated via multivariate/univariate survival analyses. Moreover, the correlation between EEF1E1 and tumor immune infiltration was analyzed using the gsva package with the ssgsea algorithm. Pearson correlation was used to investigate the correlation between EEF1E1 expression and p53 pathway genes expression. Two third-party databases were used to validate the content of EEF1E1 protein and mRNA expression patterns and prognosis analysis. The immunohistochemistry and multiplex immunohistochemistry was used to verify the bio-informatics results. RESULTS: EEF1E1 mRNA and protein expression in tumor was statistically higher than normal (EEF1E1 mRNA: p < 0.001; EEF1E1 protein: p < 0.01). Results from paired t-test (cancer and adjacent tissues) exhibited consistent trend (t = 7.572, p < 0.001). Immunohistochemistry showed that EEF1E1 is highly expressed in cancer. The expression of EEF1E1 was positively correlated with body weight, BMI, tumor status, vascular invasion, AFP, logistic grade, T stage and pathological stage. The univariate Cox model revealed that high EEF1E1 expression was strongly associated with worse OS (HR=2.581; 95% CI: 1.782-3.739; p < 0.001), as was T stage, pathologic stage, Histologic grade. High EEF1E1 expression was the only independent prognostic factor associated with OS (HR=2.57; 95% CI: 1.715-3.851; p < 0.001) in the multivariate analysis. EEF1E1 was significantly correlated with various immune cells, including cytotoxic cells, DC, macrophages, neutrophils, NK cd56bright, TFH, Tgd, Th17, Th2, Treg. Multiplex immunohistochemistry showed that the EEF1E1 protein level is positively correlated to the CD3, CD4, PD1 and is negatively correlated to the CD8. The expression level of EEF1E1 in HCC was significantly correlated with the key genes involved in the p53 pathway. The expression of EEF1E1, ATM, p53 and CASPASE3 in HCC tissues was significantly higher than that in adjacent tissues. CONCLUSION: EEF1E1 is highly expressed in cancer tissues in HCC. EEF1E1’s high expression is significantly correlated with worse prognosis and immune cell infiltration of HCC. EEF1E1 may be participating in EEF1E1/ATM/p53 signaling pathway in HCC. Frontiers Media S.A. 2021-07-02 /pmc/articles/PMC8285289/ /pubmed/34282404 http://dx.doi.org/10.3389/fonc.2021.700972 Text en Copyright © 2021 Han, Feng, Pang, Zou, Li, Geng, Li, Min and Shi 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 | Oncology Han, Ruiqin Feng, Penghui Pang, Junyi Zou, Dingfeng Li, Xiaolu Geng, Chao Li, Lili Min, Jie Shi, Jing A Novel HCC Prognosis Predictor EEF1E1 Is Related to Immune Infiltration and May Be Involved in EEF1E1/ATM/p53 Signaling |
title | A Novel HCC Prognosis Predictor EEF1E1 Is Related to Immune Infiltration and May Be Involved in EEF1E1/ATM/p53 Signaling |
title_full | A Novel HCC Prognosis Predictor EEF1E1 Is Related to Immune Infiltration and May Be Involved in EEF1E1/ATM/p53 Signaling |
title_fullStr | A Novel HCC Prognosis Predictor EEF1E1 Is Related to Immune Infiltration and May Be Involved in EEF1E1/ATM/p53 Signaling |
title_full_unstemmed | A Novel HCC Prognosis Predictor EEF1E1 Is Related to Immune Infiltration and May Be Involved in EEF1E1/ATM/p53 Signaling |
title_short | A Novel HCC Prognosis Predictor EEF1E1 Is Related to Immune Infiltration and May Be Involved in EEF1E1/ATM/p53 Signaling |
title_sort | novel hcc prognosis predictor eef1e1 is related to immune infiltration and may be involved in eef1e1/atm/p53 signaling |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285289/ https://www.ncbi.nlm.nih.gov/pubmed/34282404 http://dx.doi.org/10.3389/fonc.2021.700972 |
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