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Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma
BACKGROUND: One of the most prevalent cancers in the world is lung cancer, with adenocarcinoma (LUAD) making up a significant portion of cases. According to the National Cancer Institute (NCI), there are new cases and fatality rates per 100,000 individuals as follows: New instances of lung and bronc...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10466921/ https://www.ncbi.nlm.nih.gov/pubmed/37644544 http://dx.doi.org/10.1186/s13023-023-02807-1 |
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author | Xu, Bowen Zhang, Jingang Chen, Weigang Cai, Wei |
author_facet | Xu, Bowen Zhang, Jingang Chen, Weigang Cai, Wei |
author_sort | Xu, Bowen |
collection | PubMed |
description | BACKGROUND: One of the most prevalent cancers in the world is lung cancer, with adenocarcinoma (LUAD) making up a significant portion of cases. According to the National Cancer Institute (NCI), there are new cases and fatality rates per 100,000 individuals as follows: New instances of lung and bronchial cancer occur annually at a rate of 50.0 per 100,000 persons. The yearly death rate for men and women is 35.0 per 100,000. DNA methylation is one of the earliest discovered and widely studied epigenetic regulatory mechanisms, and its abnormality is closely related to the occurrence and development of cancer. However, the prognostic value of DNA methylation and LUAD needs to be further explored to improve the survival prediction of LUAD patients. METHODS: The transcriptome data and clinical data of LUAD were downloaded from TCGA and GEO databases, and the Illumina Human Methylation450 array (450k array) data were downloaded from the TCGA database. Firstly, the intersection of the expressed genes of the two databases is corrected, the differential analysis is performed, and the methylation data is evaluated by the MethylMix package to obtain differentially methylated genes. Independent prognostic genes were screened out using univariate and multivariate Cox regression analysis, and a methylation prognostic model was developed using univariate Cox analysis and validated with the GSE30219 dataset in the GEO database. Survival analysis between methylation high-risk and low-risk groups was performed and a methylation-based gene prognostic model was constructed. Finally, the prediction of potential drugs associated with the LUAD gene signature using Drug Sensitivity Genomics in Cancer (GDSC). RESULTS: In this study, a total of 555 samples from the TCGA database and 307 samples from GSE30219 were included, and a total of 24 differential methylation driver genes were identified. Univariate and multivariate Cox regression analyzes were used to screen out independent prognostic genes, involving 2 genes: CFTR, PKIA. Survival analysis was different between the methylation high-risk group and the low-risk group, the CFTR high methylation group and the low methylation group were poor, and the opposite was true for PKIA. CONCLUSIONS: Our study revealed that the methylation status of CFTR and PKIA can serve as potential prognostic biomarkers and therapeutic targets in lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-023-02807-1. |
format | Online Article Text |
id | pubmed-10466921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-104669212023-08-31 Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma Xu, Bowen Zhang, Jingang Chen, Weigang Cai, Wei Orphanet J Rare Dis Research BACKGROUND: One of the most prevalent cancers in the world is lung cancer, with adenocarcinoma (LUAD) making up a significant portion of cases. According to the National Cancer Institute (NCI), there are new cases and fatality rates per 100,000 individuals as follows: New instances of lung and bronchial cancer occur annually at a rate of 50.0 per 100,000 persons. The yearly death rate for men and women is 35.0 per 100,000. DNA methylation is one of the earliest discovered and widely studied epigenetic regulatory mechanisms, and its abnormality is closely related to the occurrence and development of cancer. However, the prognostic value of DNA methylation and LUAD needs to be further explored to improve the survival prediction of LUAD patients. METHODS: The transcriptome data and clinical data of LUAD were downloaded from TCGA and GEO databases, and the Illumina Human Methylation450 array (450k array) data were downloaded from the TCGA database. Firstly, the intersection of the expressed genes of the two databases is corrected, the differential analysis is performed, and the methylation data is evaluated by the MethylMix package to obtain differentially methylated genes. Independent prognostic genes were screened out using univariate and multivariate Cox regression analysis, and a methylation prognostic model was developed using univariate Cox analysis and validated with the GSE30219 dataset in the GEO database. Survival analysis between methylation high-risk and low-risk groups was performed and a methylation-based gene prognostic model was constructed. Finally, the prediction of potential drugs associated with the LUAD gene signature using Drug Sensitivity Genomics in Cancer (GDSC). RESULTS: In this study, a total of 555 samples from the TCGA database and 307 samples from GSE30219 were included, and a total of 24 differential methylation driver genes were identified. Univariate and multivariate Cox regression analyzes were used to screen out independent prognostic genes, involving 2 genes: CFTR, PKIA. Survival analysis was different between the methylation high-risk group and the low-risk group, the CFTR high methylation group and the low methylation group were poor, and the opposite was true for PKIA. CONCLUSIONS: Our study revealed that the methylation status of CFTR and PKIA can serve as potential prognostic biomarkers and therapeutic targets in lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-023-02807-1. BioMed Central 2023-08-29 /pmc/articles/PMC10466921/ /pubmed/37644544 http://dx.doi.org/10.1186/s13023-023-02807-1 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 Xu, Bowen Zhang, Jingang Chen, Weigang Cai, Wei Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma |
title | Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma |
title_full | Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma |
title_fullStr | Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma |
title_full_unstemmed | Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma |
title_short | Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma |
title_sort | exploring the methylation status of cftr and pkia genes as potential biomarkers for lung adenocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10466921/ https://www.ncbi.nlm.nih.gov/pubmed/37644544 http://dx.doi.org/10.1186/s13023-023-02807-1 |
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