Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis
Abstract Lung adenocarcinoma (LUAD) is a major contributor to cancer-related deaths, distinguished by its pronounced tumor heterogeneity and persistent challenges in overcoming drug resistance. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to dissect the roles of programmed cell...
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Springer
2024-12-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-024-01736-0 |
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| author | Long Li Shancheng He |
| author_facet | Long Li Shancheng He |
| author_sort | Long Li |
| collection | DOAJ |
| description | Abstract Lung adenocarcinoma (LUAD) is a major contributor to cancer-related deaths, distinguished by its pronounced tumor heterogeneity and persistent challenges in overcoming drug resistance. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to dissect the roles of programmed cell death (PCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, in shaping LUAD heterogeneity, immune infiltration, and prognosis. Among these, ferroptosis and pyroptosis were most significantly associated with favorable survival outcomes, highlighting their potential roles in enhancing anti-tumor immunity. Distinct PCD-related LUAD subtypes were identified, characterized by differential pathway activation and immune cell composition. Subtypes enriched with cytotoxic lymphocytes and dendritic cells demonstrated improved survival outcomes and increased potential responsiveness to immunotherapy. Drug sensitivity analysis revealed that these subtypes exhibited heightened sensitivity to targeted therapies and immune checkpoint inhibitors, suggesting opportunities for personalized treatment strategies. Our findings emphasize the interplay between PCD pathways and the tumor microenvironment, providing insights into the mechanisms underlying tumor drug resistance and immune evasion. By linking molecular and immune features to clinical outcomes, this study highlights the potential of targeting PCD pathways to enhance therapeutic efficacy and overcome resistance in LUAD. These results contribute to a growing framework for developing precise and adaptable cancer therapies tailored to specific tumor characteristics. |
| format | Article |
| id | doaj-art-b61f625fb13d43ed825e7b723f784b2a |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-b61f625fb13d43ed825e7b723f784b2a2024-12-29T12:37:37ZengSpringerDiscover Oncology2730-60112024-12-0115111310.1007/s12672-024-01736-0Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysisLong Li0Shancheng He1Department of Critical Care Medicine, The Fifth People’s Hospital of Ganzhou CityDepartment of Critical Care Medicine, The Fifth People’s Hospital of Ganzhou CityAbstract Lung adenocarcinoma (LUAD) is a major contributor to cancer-related deaths, distinguished by its pronounced tumor heterogeneity and persistent challenges in overcoming drug resistance. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to dissect the roles of programmed cell death (PCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, in shaping LUAD heterogeneity, immune infiltration, and prognosis. Among these, ferroptosis and pyroptosis were most significantly associated with favorable survival outcomes, highlighting their potential roles in enhancing anti-tumor immunity. Distinct PCD-related LUAD subtypes were identified, characterized by differential pathway activation and immune cell composition. Subtypes enriched with cytotoxic lymphocytes and dendritic cells demonstrated improved survival outcomes and increased potential responsiveness to immunotherapy. Drug sensitivity analysis revealed that these subtypes exhibited heightened sensitivity to targeted therapies and immune checkpoint inhibitors, suggesting opportunities for personalized treatment strategies. Our findings emphasize the interplay between PCD pathways and the tumor microenvironment, providing insights into the mechanisms underlying tumor drug resistance and immune evasion. By linking molecular and immune features to clinical outcomes, this study highlights the potential of targeting PCD pathways to enhance therapeutic efficacy and overcome resistance in LUAD. These results contribute to a growing framework for developing precise and adaptable cancer therapies tailored to specific tumor characteristics.https://doi.org/10.1007/s12672-024-01736-0Lung adenocarcinomaProgrammed cell deathSingle-cell RNA sequencingTumor heterogeneityDrug resistanceImmune infiltration |
| spellingShingle | Long Li Shancheng He Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis Discover Oncology Lung adenocarcinoma Programmed cell death Single-cell RNA sequencing Tumor heterogeneity Drug resistance Immune infiltration |
| title | Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis |
| title_full | Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis |
| title_fullStr | Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis |
| title_full_unstemmed | Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis |
| title_short | Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis |
| title_sort | programmed cell death pathways in lung adenocarcinoma illuminating tumor drug resistance and therapeutic opportunities through single cell analysis |
| topic | Lung adenocarcinoma Programmed cell death Single-cell RNA sequencing Tumor heterogeneity Drug resistance Immune infiltration |
| url | https://doi.org/10.1007/s12672-024-01736-0 |
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