Highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage IA risk stratification
Abstract Background The refinement of risk stratification in lung adenocarcinoma (LUAD) plays a pivotal role in advancing precision medicine; however, the current staging classification falls short of comprehensiveness, particularly in the case of stage IA patients. We aimed to molecularly stratify...
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BMC
2025-01-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-024-13308-0 |
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| author | Yanlu Xiong Yongfu Ma Jie Lei Jianfei Zhu Nianlin Xie Feng Tian Qiang Lu Miaomiao Wen Qian Zheng Yong Han Tao Jiang Yang Liu |
| author_facet | Yanlu Xiong Yongfu Ma Jie Lei Jianfei Zhu Nianlin Xie Feng Tian Qiang Lu Miaomiao Wen Qian Zheng Yong Han Tao Jiang Yang Liu |
| author_sort | Yanlu Xiong |
| collection | DOAJ |
| description | Abstract Background The refinement of risk stratification in lung adenocarcinoma (LUAD) plays a pivotal role in advancing precision medicine; however, the current staging classification falls short of comprehensiveness, particularly in the case of stage IA patients. We aimed to molecularly stratify LUAD patients especially for stage IA. Methods We analysed tumour heterogeneity and identified highly proliferating cancer cells (HPCs) in LUAD by performing single-cell RNA sequencing (scRNA-seq) analysis, immunohistochemical (IHC) staining using a tissue microarray, flow cytometry and biological experiments. Then, we quantified the content of HPCs in nine LUAD datasets by single-sample gene set enrichment analysis and evaluated the relationship between the percentage of HPCs and overall survival (OS). Next, we analysed the OS predictive effect of HPCs at different LUAD stages, especially for stage I risk stratification. Furthermore, we established a prognostic prediction model based on HPC-associated genes for clinical application. The above findings were validated in another five LUAD datasets. Finally, we explored the relationship between HPCs and the progressive pathological evolution of early-stage LUAD and the driving mutations by scRNA-seq, bulk RNA-seq and IHC staining. Results LUAD tissues carry a small proportion of HPCs, which show potential for malignant proliferation and intense interactions with the microenvironment. A high HPC content is an independent risk factor for OS in LUAD patients, even in stage IA patients. HPCs can be used to establish a cut-off point for the prognosis of stage IA disease, with patients with a higher risk showing a prognosis similar to that of patients with stage IB disease. We built an R package (HSurADs) based on HPC-associated genes, which exhibited good efficacy for the prognostic prediction of LUAD. HPCs gradually increase with the pathological evolution of early-stage LUAD, which may be affected by TP53 mutations. Conclusion The HPC content can be used as a novel prognostic factor for LUAD, especially for stage IA risk stratification. |
| format | Article |
| id | doaj-art-8f8f0811f5574c0f9c25b8e202d01d8f |
| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-8f8f0811f5574c0f9c25b8e202d01d8f2025-08-20T02:35:40ZengBMCBMC Cancer1471-24072025-01-0125111710.1186/s12885-024-13308-0Highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage IA risk stratificationYanlu Xiong0Yongfu Ma1Jie Lei2Jianfei Zhu3Nianlin Xie4Feng Tian5Qiang Lu6Miaomiao Wen7Qian Zheng8Yong Han9Tao Jiang10Yang Liu11Department of Thoracic Surgery, The First Medical Center, Chinese PLA General HospitalDepartment of Thoracic Surgery, The First Medical Center, Chinese PLA General HospitalDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, The First Medical Center, Chinese PLA General HospitalDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, The First Medical Center, Chinese PLA General HospitalAbstract Background The refinement of risk stratification in lung adenocarcinoma (LUAD) plays a pivotal role in advancing precision medicine; however, the current staging classification falls short of comprehensiveness, particularly in the case of stage IA patients. We aimed to molecularly stratify LUAD patients especially for stage IA. Methods We analysed tumour heterogeneity and identified highly proliferating cancer cells (HPCs) in LUAD by performing single-cell RNA sequencing (scRNA-seq) analysis, immunohistochemical (IHC) staining using a tissue microarray, flow cytometry and biological experiments. Then, we quantified the content of HPCs in nine LUAD datasets by single-sample gene set enrichment analysis and evaluated the relationship between the percentage of HPCs and overall survival (OS). Next, we analysed the OS predictive effect of HPCs at different LUAD stages, especially for stage I risk stratification. Furthermore, we established a prognostic prediction model based on HPC-associated genes for clinical application. The above findings were validated in another five LUAD datasets. Finally, we explored the relationship between HPCs and the progressive pathological evolution of early-stage LUAD and the driving mutations by scRNA-seq, bulk RNA-seq and IHC staining. Results LUAD tissues carry a small proportion of HPCs, which show potential for malignant proliferation and intense interactions with the microenvironment. A high HPC content is an independent risk factor for OS in LUAD patients, even in stage IA patients. HPCs can be used to establish a cut-off point for the prognosis of stage IA disease, with patients with a higher risk showing a prognosis similar to that of patients with stage IB disease. We built an R package (HSurADs) based on HPC-associated genes, which exhibited good efficacy for the prognostic prediction of LUAD. HPCs gradually increase with the pathological evolution of early-stage LUAD, which may be affected by TP53 mutations. Conclusion The HPC content can be used as a novel prognostic factor for LUAD, especially for stage IA risk stratification.https://doi.org/10.1186/s12885-024-13308-0Lung adenocarcinomaHighly proliferating cancer cellsStage IAPrognosis |
| spellingShingle | Yanlu Xiong Yongfu Ma Jie Lei Jianfei Zhu Nianlin Xie Feng Tian Qiang Lu Miaomiao Wen Qian Zheng Yong Han Tao Jiang Yang Liu Highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage IA risk stratification BMC Cancer Lung adenocarcinoma Highly proliferating cancer cells Stage IA Prognosis |
| title | Highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage IA risk stratification |
| title_full | Highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage IA risk stratification |
| title_fullStr | Highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage IA risk stratification |
| title_full_unstemmed | Highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage IA risk stratification |
| title_short | Highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage IA risk stratification |
| title_sort | highly proliferating cancer cells function as novel prognostic biomarkers for lung adenocarcinoma with particular usefulness for stage ia risk stratification |
| topic | Lung adenocarcinoma Highly proliferating cancer cells Stage IA Prognosis |
| url | https://doi.org/10.1186/s12885-024-13308-0 |
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