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Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning
BACKGROUND: Lung adenocarcinoma (LUAD) is an aggressive cancer that has an extremely poor prognosis. As well as facilitating the detachment of cancer cells from the primary tumor site, anoikis plays an important role in cancer metastasis. Few studies to date, however, have examined the role of anoik...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199682/ https://www.ncbi.nlm.nih.gov/pubmed/37213475 http://dx.doi.org/10.2147/IJGM.S409006 |
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author | Wang, Qilong Sun, Nannan Zhang, Mingzhi |
author_facet | Wang, Qilong Sun, Nannan Zhang, Mingzhi |
author_sort | Wang, Qilong |
collection | PubMed |
description | BACKGROUND: Lung adenocarcinoma (LUAD) is an aggressive cancer that has an extremely poor prognosis. As well as facilitating the detachment of cancer cells from the primary tumor site, anoikis plays an important role in cancer metastasis. Few studies to date, however, have examined the role of anoikis in LUAD, in patient prognosis. METHODS: A total of 316 anoikis-related genes (ANRGs) integrated from Genecards and Harmonizome portals. LUAD transcriptome data were retrieved from the Genotype-Tissue Expression Project (GEO) and The Cancer Genome Atlas (TCGA). Anoikis-related prognostic genes (ANRGs) were primarily screened by univariate Cox regression. All ANRGs were included in the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model to construct the powerful prognostic signature. This signature was validated and assessed using the Kaplan-Meier method as well as univariate and multivariate Cox regression analyses. Anoikis-related regulators of risk score were identified using a XG-boost machine learning model. The expression of ITGB4 protein was examined in a ZhengZhou University (ZZU) tissue cohort by immunohistochemistry, and the potential mechanisms of action of ITGB4 in LUAD were explored by GO, KEGG, and ingenuity pathway analyses and by GSEA. RESULTS: A risk score signature was constructed based on eight ANRGs, with high risk scores found to closely correlate with unfavorable clinical features. ITGB4 expression may be associated with 5-year over survival, with immunohistochemistry showed that the expression of ITGB4 was higher in LUAD than in nontumor tissues. Enrichment analysis suggested that ITGB4 may promote LUAD development by targeting E2F, MYC, and oxidative phosphorylation signaling pathways. CONCLUSION: Our anoikis-related signature from RNA-seq data may be a novel prognostic biomarker in patients with LUAD. It may help physicians develop personalized LUAD treatments in clinical practice. Moreover, ITGB4 may affect the development of LUAD through the oxidative phosphorylation pathway. |
format | Online Article Text |
id | pubmed-10199682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-101996822023-05-21 Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning Wang, Qilong Sun, Nannan Zhang, Mingzhi Int J Gen Med Original Research BACKGROUND: Lung adenocarcinoma (LUAD) is an aggressive cancer that has an extremely poor prognosis. As well as facilitating the detachment of cancer cells from the primary tumor site, anoikis plays an important role in cancer metastasis. Few studies to date, however, have examined the role of anoikis in LUAD, in patient prognosis. METHODS: A total of 316 anoikis-related genes (ANRGs) integrated from Genecards and Harmonizome portals. LUAD transcriptome data were retrieved from the Genotype-Tissue Expression Project (GEO) and The Cancer Genome Atlas (TCGA). Anoikis-related prognostic genes (ANRGs) were primarily screened by univariate Cox regression. All ANRGs were included in the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model to construct the powerful prognostic signature. This signature was validated and assessed using the Kaplan-Meier method as well as univariate and multivariate Cox regression analyses. Anoikis-related regulators of risk score were identified using a XG-boost machine learning model. The expression of ITGB4 protein was examined in a ZhengZhou University (ZZU) tissue cohort by immunohistochemistry, and the potential mechanisms of action of ITGB4 in LUAD were explored by GO, KEGG, and ingenuity pathway analyses and by GSEA. RESULTS: A risk score signature was constructed based on eight ANRGs, with high risk scores found to closely correlate with unfavorable clinical features. ITGB4 expression may be associated with 5-year over survival, with immunohistochemistry showed that the expression of ITGB4 was higher in LUAD than in nontumor tissues. Enrichment analysis suggested that ITGB4 may promote LUAD development by targeting E2F, MYC, and oxidative phosphorylation signaling pathways. CONCLUSION: Our anoikis-related signature from RNA-seq data may be a novel prognostic biomarker in patients with LUAD. It may help physicians develop personalized LUAD treatments in clinical practice. Moreover, ITGB4 may affect the development of LUAD through the oxidative phosphorylation pathway. Dove 2023-05-16 /pmc/articles/PMC10199682/ /pubmed/37213475 http://dx.doi.org/10.2147/IJGM.S409006 Text en © 2023 Wang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wang, Qilong Sun, Nannan Zhang, Mingzhi Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning |
title | Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning |
title_full | Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning |
title_fullStr | Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning |
title_full_unstemmed | Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning |
title_short | Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning |
title_sort | identification and validation of anoikis-related signatures for predicting prognosis in lung adenocarcinoma with machine learning |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199682/ https://www.ncbi.nlm.nih.gov/pubmed/37213475 http://dx.doi.org/10.2147/IJGM.S409006 |
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