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ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia
Integrin subunit alpha L (ITGAL) was found aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in acute myeloid leukemia and emphasize its associations with immunity. Here, we found ITGAL was highly expressed in...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400260/ https://www.ncbi.nlm.nih.gov/pubmed/35999614 http://dx.doi.org/10.1186/s12935-022-02684-x |
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author | Li, Ran Wu, Xiaolu Xue, Kai Li, Junmin |
author_facet | Li, Ran Wu, Xiaolu Xue, Kai Li, Junmin |
author_sort | Li, Ran |
collection | PubMed |
description | Integrin subunit alpha L (ITGAL) was found aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in acute myeloid leukemia and emphasize its associations with immunity. Here, we found ITGAL was highly expressed in AML patients and elevated expression was associated with poor prognosis. ITGAL was associated with age and cytogenetic risk classifications, but not relevant to AML driver gene mutations. Univariate and multivariate Cox regression analyses determined ITGAL as an independent prognostic factor. The nomogram integrating ITGAL and clinicopathologic variables was constructed to predict 1-, 3- and 5-year overall survival (OS). Functional analyses revealed that ITGAL was mainly responsible for the production and metabolic process of cytokine. As for immunity, ITGAL was positively associated with MDSCs including iDCs, and macrophages in the TCGA-LAML cohort. We also found that ITGAL was positively associated with most immune checkpoint genes and cytokines. In addition, we found that ITGAL knockdown caused substantial inhibition of cell growth and significant induction of early apoptosis in AML cells. The xenograft study indicated that ITGAL knockdown prolonged the survival of recipient mice. Overall, ITGAL is an independent prognostic factor and is closely related to the number of MDSCs and cytokine production. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02684-x. |
format | Online Article Text |
id | pubmed-9400260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-94002602022-08-25 ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia Li, Ran Wu, Xiaolu Xue, Kai Li, Junmin Cancer Cell Int Research Integrin subunit alpha L (ITGAL) was found aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in acute myeloid leukemia and emphasize its associations with immunity. Here, we found ITGAL was highly expressed in AML patients and elevated expression was associated with poor prognosis. ITGAL was associated with age and cytogenetic risk classifications, but not relevant to AML driver gene mutations. Univariate and multivariate Cox regression analyses determined ITGAL as an independent prognostic factor. The nomogram integrating ITGAL and clinicopathologic variables was constructed to predict 1-, 3- and 5-year overall survival (OS). Functional analyses revealed that ITGAL was mainly responsible for the production and metabolic process of cytokine. As for immunity, ITGAL was positively associated with MDSCs including iDCs, and macrophages in the TCGA-LAML cohort. We also found that ITGAL was positively associated with most immune checkpoint genes and cytokines. In addition, we found that ITGAL knockdown caused substantial inhibition of cell growth and significant induction of early apoptosis in AML cells. The xenograft study indicated that ITGAL knockdown prolonged the survival of recipient mice. Overall, ITGAL is an independent prognostic factor and is closely related to the number of MDSCs and cytokine production. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02684-x. BioMed Central 2022-08-23 /pmc/articles/PMC9400260/ /pubmed/35999614 http://dx.doi.org/10.1186/s12935-022-02684-x 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 Li, Ran Wu, Xiaolu Xue, Kai Li, Junmin ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia |
title | ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia |
title_full | ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia |
title_fullStr | ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia |
title_full_unstemmed | ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia |
title_short | ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia |
title_sort | itgal infers adverse prognosis and correlates with immunity in acute myeloid leukemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400260/ https://www.ncbi.nlm.nih.gov/pubmed/35999614 http://dx.doi.org/10.1186/s12935-022-02684-x |
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