Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma
Background: Lung adenocarcinoma (LUAD) accounts for the majority of lung cancers, and the survival of patients with advanced LUAD is poor. The extracellular matrix (ECM) is a fundamental component of the tumor microenvironment (TME) that determines the oncogenesis and antitumor immunity of solid tum...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.835043/full |
| _version_ | 1828848065925087232 |
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| author | Lingyan Xiao Qian Li Yongbiao Huang Zhijie Fan Wan Qin Bo Liu Xianglin Yuan |
| author_facet | Lingyan Xiao Qian Li Yongbiao Huang Zhijie Fan Wan Qin Bo Liu Xianglin Yuan |
| author_sort | Lingyan Xiao |
| collection | DOAJ |
| description | Background: Lung adenocarcinoma (LUAD) accounts for the majority of lung cancers, and the survival of patients with advanced LUAD is poor. The extracellular matrix (ECM) is a fundamental component of the tumor microenvironment (TME) that determines the oncogenesis and antitumor immunity of solid tumors. However, the prognostic value of extracellular matrix-related genes (ERGs) in LUAD remains unexplored. Therefore, this study is aimed to explore the prognostic value of ERGs in LUAD and establish a classification system to predict the survival of patients with LUAD.Methods: LUAD samples from The Cancer Genome Atlas (TCGA) and GSE37745 were used as discovery and validation cohorts, respectively. Prognostic ERGs were identified by univariate Cox analysis and used to construct a prognostic signature by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The extracellular matrix-related score (ECMRS) of each patient was calculated according to the prognostic signature and used to classify patients into high- and low-risk groups. The prognostic performance of the signature was evaluated using Kaplan–Meier curves, Cox regression analyses, and ROC curves. The relationship between ECMRS and tumor immunity was determined using stepwise analyses. A nomogram based on the signature was established for the convenience of use in the clinical practice. The prognostic genes were validated in multiple databases and clinical specimens by qRT-PCR.Results: A prognostic signature based on eight ERGs (FERMT1, CTSV, CPS1, ENTPD2, SERPINB5, ITGA8, ADAMTS8, and LYPD3) was constructed. Patients with higher ECMRS had poorer survival, lower immune scores, and higher tumor purity in both the discovery and validation cohorts. The predictive power of the signature was independent of the clinicopathological parameters, and the nomogram could also predict survival precisely.Conclusions: We constructed an ECM-related gene signature which can be used to predict survival and tumor immunity in patients with LUAD. This signature can serve as a novel prognostic indicator and therapeutic target in LUAD. |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T22:22:35Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-fd5ed7af069d498abff5eed680aa31732022-12-22T00:09:52ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-04-011010.3389/fcell.2022.835043835043Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung AdenocarcinomaLingyan Xiao0Qian Li1Yongbiao Huang2Zhijie Fan3Wan Qin4Bo Liu5Xianglin Yuan6Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackground: Lung adenocarcinoma (LUAD) accounts for the majority of lung cancers, and the survival of patients with advanced LUAD is poor. The extracellular matrix (ECM) is a fundamental component of the tumor microenvironment (TME) that determines the oncogenesis and antitumor immunity of solid tumors. However, the prognostic value of extracellular matrix-related genes (ERGs) in LUAD remains unexplored. Therefore, this study is aimed to explore the prognostic value of ERGs in LUAD and establish a classification system to predict the survival of patients with LUAD.Methods: LUAD samples from The Cancer Genome Atlas (TCGA) and GSE37745 were used as discovery and validation cohorts, respectively. Prognostic ERGs were identified by univariate Cox analysis and used to construct a prognostic signature by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The extracellular matrix-related score (ECMRS) of each patient was calculated according to the prognostic signature and used to classify patients into high- and low-risk groups. The prognostic performance of the signature was evaluated using Kaplan–Meier curves, Cox regression analyses, and ROC curves. The relationship between ECMRS and tumor immunity was determined using stepwise analyses. A nomogram based on the signature was established for the convenience of use in the clinical practice. The prognostic genes were validated in multiple databases and clinical specimens by qRT-PCR.Results: A prognostic signature based on eight ERGs (FERMT1, CTSV, CPS1, ENTPD2, SERPINB5, ITGA8, ADAMTS8, and LYPD3) was constructed. Patients with higher ECMRS had poorer survival, lower immune scores, and higher tumor purity in both the discovery and validation cohorts. The predictive power of the signature was independent of the clinicopathological parameters, and the nomogram could also predict survival precisely.Conclusions: We constructed an ECM-related gene signature which can be used to predict survival and tumor immunity in patients with LUAD. This signature can serve as a novel prognostic indicator and therapeutic target in LUAD.https://www.frontiersin.org/articles/10.3389/fcell.2022.835043/fulllung adenocarcinomaextracellar matrixprognostic signaturetumor micoenvironmentimmunotharapy |
| spellingShingle | Lingyan Xiao Qian Li Yongbiao Huang Zhijie Fan Wan Qin Bo Liu Xianglin Yuan Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma Frontiers in Cell and Developmental Biology lung adenocarcinoma extracellar matrix prognostic signature tumor micoenvironment immunotharapy |
| title | Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma |
| title_full | Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma |
| title_fullStr | Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma |
| title_full_unstemmed | Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma |
| title_short | Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma |
| title_sort | integrative analysis constructs an extracellular matrix associated gene signature for the prediction of survival and tumor immunity in lung adenocarcinoma |
| topic | lung adenocarcinoma extracellar matrix prognostic signature tumor micoenvironment immunotharapy |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.835043/full |
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