The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma
BackgroundThe lysosome plays a vitally crucial role in tumor development and is a major participant in the cell death process, involving aberrant functional and structural changes. However, there are few studies on lysosome-associated genes (LAGs) in lung adenocarcinoma (LUAD).MethodsBulk RNA-seq of...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2024.1497312/full |
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| author | Wuguang Chang Wuyou Gao Yawei Wu Bin Luo Lekai Zhong Leqi Zhong Wenqian Lin Zhesheng Wen Youfang Chen |
| author_facet | Wuguang Chang Wuyou Gao Yawei Wu Bin Luo Lekai Zhong Leqi Zhong Wenqian Lin Zhesheng Wen Youfang Chen |
| author_sort | Wuguang Chang |
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| description | BackgroundThe lysosome plays a vitally crucial role in tumor development and is a major participant in the cell death process, involving aberrant functional and structural changes. However, there are few studies on lysosome-associated genes (LAGs) in lung adenocarcinoma (LUAD).MethodsBulk RNA-seq of LUAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The lysosome risk signature was constructed after univariate and least absolute shrinkage and selection operator (Lasso) cox regression analysis of the TCGA training set, and its capability was validated by additional validation sets from GEO. Single cell sequencing (scRNA) was obtained from GEO to analyze the differences of lysosome risk signature at the single-cell level and the differences in the function and pathway. In vitro experiments have validated the function of CTSH in LUAD.ResultsThe risk signature contained seven key LAGs, and patients were categorized into high- and low-risk groups based on a specific calculation formula. The LAG risk signature, which accurately predicted the prognostic status of LUAD patients, was still regarded as an independent prognostic indicator in multifactorial cox regression analysis. Subsequently, the combination of the signature and key clinical information was used to construct a column-line diagram for clinical assessment, which had a high discriminatory power. Immune infiltration analysis from bulk RNA-seq and scRNA-seq indicated that the low-risk group was immune-activated and had a better benefit in the prediction of immunotherapy. Finally, we validated its role in inhibiting tumor proliferation and metastasis in LUAD cells by knockdown of CTSH.ConclusionWe defined a new biomarker that provided unique insights for individualized survival prediction and immunotherapy recommendations for LUAD patients. |
| format | Article |
| id | doaj-art-d0754d385863461ba8479c183566e417 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-d0754d385863461ba8479c183566e4172025-01-07T05:24:09ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-01-011110.3389/fmed.2024.14973121497312The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinomaWuguang Chang0Wuyou Gao1Yawei Wu2Bin Luo3Lekai Zhong4Leqi Zhong5Wenqian Lin6Zhesheng Wen7Youfang Chen8Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, ChinaDepartment of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Anesthesiology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaSchool of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaDepartment of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Anesthesiology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaBackgroundThe lysosome plays a vitally crucial role in tumor development and is a major participant in the cell death process, involving aberrant functional and structural changes. However, there are few studies on lysosome-associated genes (LAGs) in lung adenocarcinoma (LUAD).MethodsBulk RNA-seq of LUAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The lysosome risk signature was constructed after univariate and least absolute shrinkage and selection operator (Lasso) cox regression analysis of the TCGA training set, and its capability was validated by additional validation sets from GEO. Single cell sequencing (scRNA) was obtained from GEO to analyze the differences of lysosome risk signature at the single-cell level and the differences in the function and pathway. In vitro experiments have validated the function of CTSH in LUAD.ResultsThe risk signature contained seven key LAGs, and patients were categorized into high- and low-risk groups based on a specific calculation formula. The LAG risk signature, which accurately predicted the prognostic status of LUAD patients, was still regarded as an independent prognostic indicator in multifactorial cox regression analysis. Subsequently, the combination of the signature and key clinical information was used to construct a column-line diagram for clinical assessment, which had a high discriminatory power. Immune infiltration analysis from bulk RNA-seq and scRNA-seq indicated that the low-risk group was immune-activated and had a better benefit in the prediction of immunotherapy. Finally, we validated its role in inhibiting tumor proliferation and metastasis in LUAD cells by knockdown of CTSH.ConclusionWe defined a new biomarker that provided unique insights for individualized survival prediction and immunotherapy recommendations for LUAD patients.https://www.frontiersin.org/articles/10.3389/fmed.2024.1497312/fulllysosomeprognostic modelCTSHlung adenocarcinomaimmunotherapy |
| spellingShingle | Wuguang Chang Wuyou Gao Yawei Wu Bin Luo Lekai Zhong Leqi Zhong Wenqian Lin Zhesheng Wen Youfang Chen The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma Frontiers in Medicine lysosome prognostic model CTSH lung adenocarcinoma immunotherapy |
| title | The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma |
| title_full | The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma |
| title_fullStr | The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma |
| title_full_unstemmed | The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma |
| title_short | The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma |
| title_sort | lysosome related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma |
| topic | lysosome prognostic model CTSH lung adenocarcinoma immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1497312/full |
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