Integrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinoma
Abstract Non-small cell lung cancer (NSCLC), half of which are lung adenocarcinoma (LUAD), is one of the most widely spread cancers in the world. Telomerase, which maintains telomere length and chromosomal integrity, enables cancer cells to avoid replicative senescence. When telomerase is inhibited,...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85758-w |
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| author | Fengqiang Yu Liangyu Zhang Xun Zhang Jianshen Zeng Fancai Lai |
| author_facet | Fengqiang Yu Liangyu Zhang Xun Zhang Jianshen Zeng Fancai Lai |
| author_sort | Fengqiang Yu |
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| description | Abstract Non-small cell lung cancer (NSCLC), half of which are lung adenocarcinoma (LUAD), is one of the most widely spread cancers in the world. Telomerase, which maintains telomere length and chromosomal integrity, enables cancer cells to avoid replicative senescence. When telomerase is inhibited, cancer cells’ senescence began, preventing them from growing indefinitely. Cellular senescence and telomeres are intrinsically linked. As of yet, still laking a systematic study of the involvement of telomere-senescence related genes in lung adenocarcinoma development. In this study, myeloid cells were identified as the cell type which are most correlated with cellular senescence based on its highest telomere-related gene activity. GO, KEGG, GSEA and GSVA analyses were used to explore the biological function of telomere-senescence related genes in LUAD. The combined analysis of single-cell RNA-sequencing and bulk-RNA sequencing identified a gene signature composed of 14 genes which can accurately predict the prognosis of patients with LUAD. In one training and four validation sets, patients with higher Telomere Related Gene Signature (TRGS) had a worse prognosis than those with lower TRGS. Different TRGS patient groups showed varying degrees of immune cell infiltration, frequency of gene missense mutation, sensitivity to different drugs, and tumor mutation burden (TMB). Collectively, we developed a brand new signature composed of telomere-senescence related genes that can accurately predicts patients’ prognosis in LUAD, which provides new insights for future research into the role of cellular senescence in LUAD. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-9d078e2483644dc9ab2117b0dc813cb82025-01-12T12:17:46ZengNature PortfolioScientific Reports2045-23222025-01-0115112110.1038/s41598-025-85758-wIntegrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinomaFengqiang Yu0Liangyu Zhang1Xun Zhang2Jianshen Zeng3Fancai Lai4Department of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical UniversityAbstract Non-small cell lung cancer (NSCLC), half of which are lung adenocarcinoma (LUAD), is one of the most widely spread cancers in the world. Telomerase, which maintains telomere length and chromosomal integrity, enables cancer cells to avoid replicative senescence. When telomerase is inhibited, cancer cells’ senescence began, preventing them from growing indefinitely. Cellular senescence and telomeres are intrinsically linked. As of yet, still laking a systematic study of the involvement of telomere-senescence related genes in lung adenocarcinoma development. In this study, myeloid cells were identified as the cell type which are most correlated with cellular senescence based on its highest telomere-related gene activity. GO, KEGG, GSEA and GSVA analyses were used to explore the biological function of telomere-senescence related genes in LUAD. The combined analysis of single-cell RNA-sequencing and bulk-RNA sequencing identified a gene signature composed of 14 genes which can accurately predict the prognosis of patients with LUAD. In one training and four validation sets, patients with higher Telomere Related Gene Signature (TRGS) had a worse prognosis than those with lower TRGS. Different TRGS patient groups showed varying degrees of immune cell infiltration, frequency of gene missense mutation, sensitivity to different drugs, and tumor mutation burden (TMB). Collectively, we developed a brand new signature composed of telomere-senescence related genes that can accurately predicts patients’ prognosis in LUAD, which provides new insights for future research into the role of cellular senescence in LUAD.https://doi.org/10.1038/s41598-025-85758-wCellular senescenceTelomereLung cancerSingle-cellPrognosis biomarker |
| spellingShingle | Fengqiang Yu Liangyu Zhang Xun Zhang Jianshen Zeng Fancai Lai Integrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinoma Scientific Reports Cellular senescence Telomere Lung cancer Single-cell Prognosis biomarker |
| title | Integrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinoma |
| title_full | Integrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinoma |
| title_fullStr | Integrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinoma |
| title_full_unstemmed | Integrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinoma |
| title_short | Integrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinoma |
| title_sort | integrated analysis of single cell and bulk rna sequencing for the cellular senescence in prognosis of lung adenocarcinoma |
| topic | Cellular senescence Telomere Lung cancer Single-cell Prognosis biomarker |
| url | https://doi.org/10.1038/s41598-025-85758-w |
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