A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma
Abstract Lung adenocarcinoma (LUAD) is a leading cause of cancer-related death, and reliable biomarkers for prognosis and treatment guidance remain limited. Membrane proteins play key roles in tumor progression and therapeutic response, yet their clinical utility in LUAD remains underexplored. We in...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-11105-8 |
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| author | Biao Tu Jun Wu Wei Zhang Haitao Tang Tenghui Dai Bingfeng Xie |
| author_facet | Biao Tu Jun Wu Wei Zhang Haitao Tang Tenghui Dai Bingfeng Xie |
| author_sort | Biao Tu |
| collection | DOAJ |
| description | Abstract Lung adenocarcinoma (LUAD) is a leading cause of cancer-related death, and reliable biomarkers for prognosis and treatment guidance remain limited. Membrane proteins play key roles in tumor progression and therapeutic response, yet their clinical utility in LUAD remains underexplored. We integrated scRNA-seq, spatial transcriptomics, and bulk RNA-seq datasets from multiple LUAD cohorts to identify cancer-specific membrane proteins derived from epithelial subpopulations. Based on these results, we constructed a prognostic signature, LCaMPS, and evaluated its predictive performance using multiple datasets. The expression of model genes was confirmed at both the bulk RNA and protein levels. Associations with the tumor microenvironment (TME) and drug sensitivity were further analyzed. A distinct LUAD-enriched epithelial cluster (Epi_c0) exhibiting hypoxic and EMT signatures was identified. 35 cancer-specific membrane proteins were defined, several of which, including TSPAN8, BACE2, and COX16, showed strong spatial localization within the tumor regions. LCaMPS, a 9-membrane gene-based prognostic model, stratified patient prognosis and predicted 5- and 10-year survival rates with high accuracy. High LCaMPS scores were associated with increased infiltration of neutrophils, endothelial cells, and fibroblasts in the TME and predicted higher sensitivity to 66 chemotherapeutic agents, including Gemcitabine and Sorafenib. Low-risk patients were predicted to respond better to drugs, such as Cisplatin and Parthenolide. This study highlights the importance of membrane expression patterns in LUAD at single-cell and spatial resolution. The LCaMPS model provides a robust prognostic and therapeutic stratification tool with potential applications in personalized cancer management. |
| format | Article |
| id | doaj-art-cbca2b17063a4ec9b42c4a58d7ddfff8 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-cbca2b17063a4ec9b42c4a58d7ddfff82025-08-20T03:42:22ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-11105-8A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinomaBiao Tu0Jun Wu1Wei Zhang2Haitao Tang3Tenghui Dai4Bingfeng Xie5Department of Cardiothoracic Surgery, The First Hospital of ChangshaSchool of Biomedical Science, Hunan UniversityInstitute for Brain Research and Rehabilitation, South China Normal UniversityDepartment of Cardiothoracic Surgery, The First Hospital of ChangshaInstitute for Brain Research and Rehabilitation, South China Normal UniversityDepartment of Cardiothoracic Surgery, The First Hospital of ChangshaAbstract Lung adenocarcinoma (LUAD) is a leading cause of cancer-related death, and reliable biomarkers for prognosis and treatment guidance remain limited. Membrane proteins play key roles in tumor progression and therapeutic response, yet their clinical utility in LUAD remains underexplored. We integrated scRNA-seq, spatial transcriptomics, and bulk RNA-seq datasets from multiple LUAD cohorts to identify cancer-specific membrane proteins derived from epithelial subpopulations. Based on these results, we constructed a prognostic signature, LCaMPS, and evaluated its predictive performance using multiple datasets. The expression of model genes was confirmed at both the bulk RNA and protein levels. Associations with the tumor microenvironment (TME) and drug sensitivity were further analyzed. A distinct LUAD-enriched epithelial cluster (Epi_c0) exhibiting hypoxic and EMT signatures was identified. 35 cancer-specific membrane proteins were defined, several of which, including TSPAN8, BACE2, and COX16, showed strong spatial localization within the tumor regions. LCaMPS, a 9-membrane gene-based prognostic model, stratified patient prognosis and predicted 5- and 10-year survival rates with high accuracy. High LCaMPS scores were associated with increased infiltration of neutrophils, endothelial cells, and fibroblasts in the TME and predicted higher sensitivity to 66 chemotherapeutic agents, including Gemcitabine and Sorafenib. Low-risk patients were predicted to respond better to drugs, such as Cisplatin and Parthenolide. This study highlights the importance of membrane expression patterns in LUAD at single-cell and spatial resolution. The LCaMPS model provides a robust prognostic and therapeutic stratification tool with potential applications in personalized cancer management.https://doi.org/10.1038/s41598-025-11105-8MembranescRNA-seqSpatial transcriptomicsPrognosisLung adenocarcinoma |
| spellingShingle | Biao Tu Jun Wu Wei Zhang Haitao Tang Tenghui Dai Bingfeng Xie A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma Scientific Reports Membrane scRNA-seq Spatial transcriptomics Prognosis Lung adenocarcinoma |
| title | A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma |
| title_full | A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma |
| title_fullStr | A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma |
| title_full_unstemmed | A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma |
| title_short | A novel cancer-associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma |
| title_sort | novel cancer associated membrane signature predicts prognosis and therapeutic response for lung adenocarcinoma |
| topic | Membrane scRNA-seq Spatial transcriptomics Prognosis Lung adenocarcinoma |
| url | https://doi.org/10.1038/s41598-025-11105-8 |
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