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Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma
BACKGROUND: Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs)...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276918/ https://www.ncbi.nlm.nih.gov/pubmed/37330494 http://dx.doi.org/10.1186/s12885-023-11042-7 |
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author | Zhang, Xiaoling Zhou, Yuxin Hu, Jiahe Yu, Xuefeng Xu, Haitao Ba, Zhichang Zhang, Haoxin Sun, Yanan Wang, Rongfang Du, Xinlian Mou, Ruishu Li, Xuedong Zhu, Jiuxin Xie, Rui |
author_facet | Zhang, Xiaoling Zhou, Yuxin Hu, Jiahe Yu, Xuefeng Xu, Haitao Ba, Zhichang Zhang, Haoxin Sun, Yanan Wang, Rongfang Du, Xinlian Mou, Ruishu Li, Xuedong Zhu, Jiuxin Xie, Rui |
author_sort | Zhang, Xiaoling |
collection | PubMed |
description | BACKGROUND: Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. METHODS: Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. RESULTS: Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT expression was positively correlated with diverse immunological characteristics, such as immune cell infiltration, cancer-immunity cycle, immunotherapy-predicted pathways, and inhibitory immune checkpoints. Submap analysis demonstrated that DLAT-high patients were more responsive to immunotherapeutic agents. Notably, the DLAT-based risk score model possessed high accuracy in predicting prognosis. Finally, the upregulated expression of DLAT was verified by RT-qPCR and IHC assays. CONCLUSIONS: We developed a DLAT-based model to predict patients’ clinical outcomes and demonstrated that DLAT was a promising prognostic and immunological biomarker in PAAD, thereby providing a new possibility for tumor therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11042-7 |
format | Online Article Text |
id | pubmed-10276918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-102769182023-06-19 Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma Zhang, Xiaoling Zhou, Yuxin Hu, Jiahe Yu, Xuefeng Xu, Haitao Ba, Zhichang Zhang, Haoxin Sun, Yanan Wang, Rongfang Du, Xinlian Mou, Ruishu Li, Xuedong Zhu, Jiuxin Xie, Rui BMC Cancer Research BACKGROUND: Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. METHODS: Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. RESULTS: Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT expression was positively correlated with diverse immunological characteristics, such as immune cell infiltration, cancer-immunity cycle, immunotherapy-predicted pathways, and inhibitory immune checkpoints. Submap analysis demonstrated that DLAT-high patients were more responsive to immunotherapeutic agents. Notably, the DLAT-based risk score model possessed high accuracy in predicting prognosis. Finally, the upregulated expression of DLAT was verified by RT-qPCR and IHC assays. CONCLUSIONS: We developed a DLAT-based model to predict patients’ clinical outcomes and demonstrated that DLAT was a promising prognostic and immunological biomarker in PAAD, thereby providing a new possibility for tumor therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11042-7 BioMed Central 2023-06-17 /pmc/articles/PMC10276918/ /pubmed/37330494 http://dx.doi.org/10.1186/s12885-023-11042-7 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/) . 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 Zhang, Xiaoling Zhou, Yuxin Hu, Jiahe Yu, Xuefeng Xu, Haitao Ba, Zhichang Zhang, Haoxin Sun, Yanan Wang, Rongfang Du, Xinlian Mou, Ruishu Li, Xuedong Zhu, Jiuxin Xie, Rui Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma |
title | Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma |
title_full | Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma |
title_fullStr | Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma |
title_full_unstemmed | Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma |
title_short | Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma |
title_sort | comprehensive analysis identifies cuproptosis-related gene dlat as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276918/ https://www.ncbi.nlm.nih.gov/pubmed/37330494 http://dx.doi.org/10.1186/s12885-023-11042-7 |
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