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The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma
Cuproptosis is a recently described copper-dependent cell death pathway. Consequently, there are still few studies on lung adenocarcinoma (LUAD)-related cuproptosis, and we aimed to deepen in this matter. In this study, data from 503 patients with lung cancer from the TCGA-LUAD cohort data collectio...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363522/ https://www.ncbi.nlm.nih.gov/pubmed/37481739 http://dx.doi.org/10.1007/s12672-023-00755-7 |
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author | Lin, Weixian Wang, Jiaren Ge, Jing Zhou, Rui Hu, Yahui Xiao, Lushan Peng, Quanzhou Zheng, Zemao |
author_facet | Lin, Weixian Wang, Jiaren Ge, Jing Zhou, Rui Hu, Yahui Xiao, Lushan Peng, Quanzhou Zheng, Zemao |
author_sort | Lin, Weixian |
collection | PubMed |
description | Cuproptosis is a recently described copper-dependent cell death pathway. Consequently, there are still few studies on lung adenocarcinoma (LUAD)-related cuproptosis, and we aimed to deepen in this matter. In this study, data from 503 patients with lung cancer from the TCGA-LUAD cohort data collection and 11 LUAD single-cells from GSE131907 as well as from 10 genes associated with cuproptosis were analyzed. The AUCell R package was used to determine the copper-dependent cell death pathway activity for each cell subpopulation, calculate the CellChat score, and display cell communication for each cell subpopulation. The PROGENy score was calculated to show the scores of tumor-related pathways in different cell populations. GO and KEGG analyses were used to calculate pathway activity. Univariate COX and random forest analyses were used to screen prognosis-associated genes and construct models. The ssGSEA and xCell algorithms were used to calculate the immunocyte infiltration score. Based on data from the GDSC database, the drug sensitivity score was calculated using oncoPredict. Finally, in vitro experiments were performed to determine the role of TLE1, the most important gene in the prognostic model. The 11 LUAD single-cell samples were classified into 8 different cell populations, from which epithelial cells showed the highest copper-dependent cell death pathway activity. Epithelial cell subsets were significantly positively correlated with MAKP, hypoxia, and other pathways. In addition, cell subgroup communication showed highly active collagen and APP pathways. Using the Findmark algorithm, differentially expressed genes (DEGs) between epithelial and other cell types were identified. Combined with the bulk data in the TCGA-LUAD database, DEGs were enriched in pathways such as EGFR tyrosine kinase inhibitor resistance, Hippo signaling pathway, and tight junction. Subsequently, we selected 4 genes (out of 112) with prognostic significance, ANKRD29, RHOV, TLE1, and NPAS2, and used them to construct a prognostic model. The high- and low-risk groups, distinguished by the median risk score, showed significantly different prognoses. Finally, we chose TLE1 as a biomarker based on the relative importance score in the prognostic model. In vitro experiments showed that TLE1 promotes tumor proliferation and migration and inhibits apoptosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-023-00755-7. |
format | Online Article Text |
id | pubmed-10363522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-103635222023-07-25 The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma Lin, Weixian Wang, Jiaren Ge, Jing Zhou, Rui Hu, Yahui Xiao, Lushan Peng, Quanzhou Zheng, Zemao Discov Oncol Research Cuproptosis is a recently described copper-dependent cell death pathway. Consequently, there are still few studies on lung adenocarcinoma (LUAD)-related cuproptosis, and we aimed to deepen in this matter. In this study, data from 503 patients with lung cancer from the TCGA-LUAD cohort data collection and 11 LUAD single-cells from GSE131907 as well as from 10 genes associated with cuproptosis were analyzed. The AUCell R package was used to determine the copper-dependent cell death pathway activity for each cell subpopulation, calculate the CellChat score, and display cell communication for each cell subpopulation. The PROGENy score was calculated to show the scores of tumor-related pathways in different cell populations. GO and KEGG analyses were used to calculate pathway activity. Univariate COX and random forest analyses were used to screen prognosis-associated genes and construct models. The ssGSEA and xCell algorithms were used to calculate the immunocyte infiltration score. Based on data from the GDSC database, the drug sensitivity score was calculated using oncoPredict. Finally, in vitro experiments were performed to determine the role of TLE1, the most important gene in the prognostic model. The 11 LUAD single-cell samples were classified into 8 different cell populations, from which epithelial cells showed the highest copper-dependent cell death pathway activity. Epithelial cell subsets were significantly positively correlated with MAKP, hypoxia, and other pathways. In addition, cell subgroup communication showed highly active collagen and APP pathways. Using the Findmark algorithm, differentially expressed genes (DEGs) between epithelial and other cell types were identified. Combined with the bulk data in the TCGA-LUAD database, DEGs were enriched in pathways such as EGFR tyrosine kinase inhibitor resistance, Hippo signaling pathway, and tight junction. Subsequently, we selected 4 genes (out of 112) with prognostic significance, ANKRD29, RHOV, TLE1, and NPAS2, and used them to construct a prognostic model. The high- and low-risk groups, distinguished by the median risk score, showed significantly different prognoses. Finally, we chose TLE1 as a biomarker based on the relative importance score in the prognostic model. In vitro experiments showed that TLE1 promotes tumor proliferation and migration and inhibits apoptosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-023-00755-7. Springer US 2023-07-23 /pmc/articles/PMC10363522/ /pubmed/37481739 http://dx.doi.org/10.1007/s12672-023-00755-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . |
spellingShingle | Research Lin, Weixian Wang, Jiaren Ge, Jing Zhou, Rui Hu, Yahui Xiao, Lushan Peng, Quanzhou Zheng, Zemao The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma |
title | The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma |
title_full | The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma |
title_fullStr | The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma |
title_full_unstemmed | The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma |
title_short | The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma |
title_sort | activity of cuproptosis pathway calculated by aucell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363522/ https://www.ncbi.nlm.nih.gov/pubmed/37481739 http://dx.doi.org/10.1007/s12672-023-00755-7 |
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