Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomes
Background: Lung adenocarcinoma (LUAD) is characterized by low overall survival rates. This research aims to explore the association between long non-coding RNAs (lncRNAs) and chromatin histone methylation/demethylation modifiers in LUAD. Methods: Datasets from The Cancer Genome Atlas (TCGA), Molecu...
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Elsevier
2025-08-01
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| Serie: | Medicine in Omics |
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| Länkar: | http://www.sciencedirect.com/science/article/pii/S2590124925000057 |
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| _version_ | 1839630851674996736 |
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| author | Xiao Zhu Zhuolong Xiong |
| author_facet | Xiao Zhu Zhuolong Xiong |
| author_sort | Xiao Zhu |
| collection | DOAJ |
| description | Background: Lung adenocarcinoma (LUAD) is characterized by low overall survival rates. This research aims to explore the association between long non-coding RNAs (lncRNAs) and chromatin histone methylation/demethylation modifiers in LUAD. Methods: Datasets from The Cancer Genome Atlas (TCGA), Molecular Signatures Database (MSigDB), and IEU Open genome-wide association studies (GWAS) database were analyzed. A prognostic risk model for LUAD was developed based on 32 lncRNAs linked to histone modification. The relationship between lncRNAs and the high-risk group of lung cancer was evaluated, and GO/KEGG analysis was conducted to investigate the connection between chromatin histone modification-related lncRNAs and biological processes/pathways. Mendelian Randomization methods, including Inverse Variance Weighted (IVW) and Bayesian Weighted Mendelian Randomization (BWMR), were employed to validate the GO/KEGG results. MR-Egger intercept test, Cochran’s Q test, and leave-one-out Analysis were utilized to assess the sensitivity of Mendelian Randomization analysis. Tumor mutation burden (TMB) analysis was performed to evaluate the prognostic impact of high-risk patients with high TMB. Results: Identified lncRNAs, including AC025741.1 and NHS-AS1, demonstrated strong associations with the high-risk group. GO/KEGG analysis revealed significant correlations between chromatin histone modification-related lncRNAs and microtubule-based movement and cytochrome enzyme P450. Response to the renin-angiotensin agents is a protective factor for lung cancer, while response to glucocorticoids is a risk factor for lung cancer. Immunomarkers MDSC, CAF, and Exclusion showed positive correlations with the risk score, and the combined effects of CAF and MDSC were found to play a pivotal role in LUAD development and progression. Conclusion: Our study not only establishes a promising LUAD prognostic risk model with potential implications for immunotherapy but also identifies lncRNAs as immune markers for LUAD immunotherapy. Additionally, we validate the causal relationship between chromatin histone methylation-related pathways and lung cancer, bolstering our understanding from a genetic perspective and opening avenues for targeted interventions in LUAD treatment. |
| format | Article |
| id | doaj-art-e7c58b0e203149faa99fe58b4a9fbbe3 |
| institution | Matheson Library |
| issn | 2590-1249 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Medicine in Omics |
| spelling | doaj-art-e7c58b0e203149faa99fe58b4a9fbbe32025-07-13T04:54:54ZengElsevierMedicine in Omics2590-12492025-08-0114100045Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomesXiao Zhu0Zhuolong Xiong1The Second Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China; Corresponding author at: Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.Background: Lung adenocarcinoma (LUAD) is characterized by low overall survival rates. This research aims to explore the association between long non-coding RNAs (lncRNAs) and chromatin histone methylation/demethylation modifiers in LUAD. Methods: Datasets from The Cancer Genome Atlas (TCGA), Molecular Signatures Database (MSigDB), and IEU Open genome-wide association studies (GWAS) database were analyzed. A prognostic risk model for LUAD was developed based on 32 lncRNAs linked to histone modification. The relationship between lncRNAs and the high-risk group of lung cancer was evaluated, and GO/KEGG analysis was conducted to investigate the connection between chromatin histone modification-related lncRNAs and biological processes/pathways. Mendelian Randomization methods, including Inverse Variance Weighted (IVW) and Bayesian Weighted Mendelian Randomization (BWMR), were employed to validate the GO/KEGG results. MR-Egger intercept test, Cochran’s Q test, and leave-one-out Analysis were utilized to assess the sensitivity of Mendelian Randomization analysis. Tumor mutation burden (TMB) analysis was performed to evaluate the prognostic impact of high-risk patients with high TMB. Results: Identified lncRNAs, including AC025741.1 and NHS-AS1, demonstrated strong associations with the high-risk group. GO/KEGG analysis revealed significant correlations between chromatin histone modification-related lncRNAs and microtubule-based movement and cytochrome enzyme P450. Response to the renin-angiotensin agents is a protective factor for lung cancer, while response to glucocorticoids is a risk factor for lung cancer. Immunomarkers MDSC, CAF, and Exclusion showed positive correlations with the risk score, and the combined effects of CAF and MDSC were found to play a pivotal role in LUAD development and progression. Conclusion: Our study not only establishes a promising LUAD prognostic risk model with potential implications for immunotherapy but also identifies lncRNAs as immune markers for LUAD immunotherapy. Additionally, we validate the causal relationship between chromatin histone methylation-related pathways and lung cancer, bolstering our understanding from a genetic perspective and opening avenues for targeted interventions in LUAD treatment.http://www.sciencedirect.com/science/article/pii/S2590124925000057Lung adenocarcinomaGWASHistone methylationHistone demethylationMendelian randomization |
| spellingShingle | Xiao Zhu Zhuolong Xiong Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomes Medicine in Omics Lung adenocarcinoma GWAS Histone methylation Histone demethylation Mendelian randomization |
| title | Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomes |
| title_full | Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomes |
| title_fullStr | Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomes |
| title_full_unstemmed | Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomes |
| title_short | Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomes |
| title_sort | multi omics integration reveals chromatin associated lncrna prognostic model in lung adenocarcinoma bridging gwas transcriptome and clinical outcomes |
| topic | Lung adenocarcinoma GWAS Histone methylation Histone demethylation Mendelian randomization |
| url | http://www.sciencedirect.com/science/article/pii/S2590124925000057 |
| work_keys_str_mv | AT xiaozhu multiomicsintegrationrevealschromatinassociatedlncrnaprognosticmodelinlungadenocarcinomabridginggwastranscriptomeandclinicaloutcomes AT zhuolongxiong multiomicsintegrationrevealschromatinassociatedlncrnaprognosticmodelinlungadenocarcinomabridginggwastranscriptomeandclinicaloutcomes |