Identification of a coagulation‐related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma
Abstract Background Lung adenocarcinoma (LUAD) is a fatal form of lung cancer with a poor prognosis. Coagulation system had been confirmed closely related to tumor progression and the hypercoagulable state encouraged the immune infiltration and development of tumor cells, leading to a poor prognosis...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.15121 |
| _version_ | 1827671527008501760 |
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| author | Siqian Yang Shiqi Chen Yue Zhao Tao Wu Yuquan Wang Tingting Li Liwan Fu Ting Ye Yue‐Qing Hu Haiquan Chen |
| author_facet | Siqian Yang Shiqi Chen Yue Zhao Tao Wu Yuquan Wang Tingting Li Liwan Fu Ting Ye Yue‐Qing Hu Haiquan Chen |
| author_sort | Siqian Yang |
| collection | DOAJ |
| description | Abstract Background Lung adenocarcinoma (LUAD) is a fatal form of lung cancer with a poor prognosis. Coagulation system had been confirmed closely related to tumor progression and the hypercoagulable state encouraged the immune infiltration and development of tumor cells, leading to a poor prognosis in cancer patients. However, the use of the coagulation‐related genes (CRGs) for prognosis in LUAD has yet to be determined. In this study, we constructed an immune‐related signature (CRRS) and identified a potential coagulation‐related biomarker (P2RX1). Methods We obtained a total of 209 CRGs based on two coagulation‐related KEGG pathways, then developed the CRRS signature by using the TCGA‐LUAD RNA‐seq data via the procedure of LASSO‐Cox regression, stepwise‐Cox regression, univariate and multivariate Cox regression. Grouped by the CRRS, Kaplan–Meier survival curves and receiver operating characteristic curves were drawn for the training and validation sets, respectively. In addition, single‐sample gene set enrichment analysis was exploited to explore immune infiltration level. Moreover, immunophenotypes and immunotherapy grouped by CRRS were further analyzed. Results We developed an immune‐related signature (CRRS) composed of COL1A2, F2, PLAUR, C4BPA, and P2RX1 in LUAD. CRRS was an independent risk factor for overall survival and displayed stable and powerful performance. Additionally, CRRS possessed distinctly superior accuracy than traditional clinical variables and molecular features. Functional analysis indicated that the differentially high expressed genes in the low‐risk group significantly enriched in T cell and B cell receptor signaling pathways. The low‐risk group was sensitive to anti‐PD‐1/PD‐L1 immunotherapy and displayed abundant immune infiltration and immune checkpoint gene expression. Finally, we identified an independent prognostic gene P2RX1. Low expression of P2RX1 associated with poor overall survival and decreased immune infiltration. Conclusions Our study revealed a significant correlation between CRRS and immune infiltration. CRRS could serve as a promising tool to improve the clinical outcomes for individual LUAD patients. |
| first_indexed | 2024-03-10T03:43:09Z |
| format | Article |
| id | doaj.art-9211a39ca30d442e942bcc0c2eb44e50 |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-03-10T03:43:09Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-9211a39ca30d442e942bcc0c2eb44e502023-11-23T09:13:55ZengWileyThoracic Cancer1759-77061759-77142023-11-0114333295330810.1111/1759-7714.15121Identification of a coagulation‐related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinomaSiqian Yang0Shiqi Chen1Yue Zhao2Tao Wu3Yuquan Wang4Tingting Li5Liwan Fu6Ting Ye7Yue‐Qing Hu8Haiquan Chen9Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaSheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Science and Biotechnology Shanghai Jiao Tong University Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaCenter for Non‐communicable Disease Management Beijing Children's Hospital Beijing ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaAbstract Background Lung adenocarcinoma (LUAD) is a fatal form of lung cancer with a poor prognosis. Coagulation system had been confirmed closely related to tumor progression and the hypercoagulable state encouraged the immune infiltration and development of tumor cells, leading to a poor prognosis in cancer patients. However, the use of the coagulation‐related genes (CRGs) for prognosis in LUAD has yet to be determined. In this study, we constructed an immune‐related signature (CRRS) and identified a potential coagulation‐related biomarker (P2RX1). Methods We obtained a total of 209 CRGs based on two coagulation‐related KEGG pathways, then developed the CRRS signature by using the TCGA‐LUAD RNA‐seq data via the procedure of LASSO‐Cox regression, stepwise‐Cox regression, univariate and multivariate Cox regression. Grouped by the CRRS, Kaplan–Meier survival curves and receiver operating characteristic curves were drawn for the training and validation sets, respectively. In addition, single‐sample gene set enrichment analysis was exploited to explore immune infiltration level. Moreover, immunophenotypes and immunotherapy grouped by CRRS were further analyzed. Results We developed an immune‐related signature (CRRS) composed of COL1A2, F2, PLAUR, C4BPA, and P2RX1 in LUAD. CRRS was an independent risk factor for overall survival and displayed stable and powerful performance. Additionally, CRRS possessed distinctly superior accuracy than traditional clinical variables and molecular features. Functional analysis indicated that the differentially high expressed genes in the low‐risk group significantly enriched in T cell and B cell receptor signaling pathways. The low‐risk group was sensitive to anti‐PD‐1/PD‐L1 immunotherapy and displayed abundant immune infiltration and immune checkpoint gene expression. Finally, we identified an independent prognostic gene P2RX1. Low expression of P2RX1 associated with poor overall survival and decreased immune infiltration. Conclusions Our study revealed a significant correlation between CRRS and immune infiltration. CRRS could serve as a promising tool to improve the clinical outcomes for individual LUAD patients.https://doi.org/10.1111/1759-7714.15121coagulation‐related genesimmune infiltrationimmunotherapylung adenocarcinomaprognosis |
| spellingShingle | Siqian Yang Shiqi Chen Yue Zhao Tao Wu Yuquan Wang Tingting Li Liwan Fu Ting Ye Yue‐Qing Hu Haiquan Chen Identification of a coagulation‐related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma Thoracic Cancer coagulation‐related genes immune infiltration immunotherapy lung adenocarcinoma prognosis |
| title | Identification of a coagulation‐related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma |
| title_full | Identification of a coagulation‐related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma |
| title_fullStr | Identification of a coagulation‐related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma |
| title_full_unstemmed | Identification of a coagulation‐related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma |
| title_short | Identification of a coagulation‐related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma |
| title_sort | identification of a coagulation related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma |
| topic | coagulation‐related genes immune infiltration immunotherapy lung adenocarcinoma prognosis |
| url | https://doi.org/10.1111/1759-7714.15121 |
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