Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma
BackgroundLung adenocarcinoma (LUAD) is a malignant tumor that seriously affects the prognosis of patients. Tumor-associated macrophages (TAMs) play a vital role in the tumor microenvironment and can be used as a potential target for tumor therapy, and phagocytosis regulators (PRs) are particularly...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.988332/full |
| _version_ | 1798046366139678720 |
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| author | Jingyang Li Qinyun Du Jiayi Sun Li Xiang Shaohui Wang |
| author_facet | Jingyang Li Qinyun Du Jiayi Sun Li Xiang Shaohui Wang |
| author_sort | Jingyang Li |
| collection | DOAJ |
| description | BackgroundLung adenocarcinoma (LUAD) is a malignant tumor that seriously affects the prognosis of patients. Tumor-associated macrophages (TAMs) play a vital role in the tumor microenvironment and can be used as a potential target for tumor therapy, and phagocytosis regulators (PRs) are particularly important in this process. However, the PRs-related signature that can predict the potential prognostic and immunotherapeutic value in patients with LUAD has not been discovered.MethodsIn this study, we mainly analyzed the effect of phagocytosis regulators on the prognosis of LUAD, and based on multiple screening analyses including differential analysis, univariate Cox analysis, and Lasso analysis, we constructed a prognostic risk model consisting of five genes. To verify the stability of the model, survival analysis and ROC curve verification were carried out through multiple data sets. In addition, we also combined many factors, such as immune infiltrating cells, clinical grouping characteristics, immune examination sites, pro-inflammatory factors, and other factors as well as in vitro cell experiments and clinical tissue samples for further validation analysis.ResultsAfter identifying 29 differentially expressed PRs in LUAD samples, we further constructed a prognostic model consisting of five prognostic signatures (FURIN, KIF23, SASH3, GNPNAT1, and ITGAL). Further survival analysis tests, ROC verification, as well as univariate and multivariate Cox regression analysis showed that the risk score of the model could well predict the prognosis of LUAD patients and could be used as an independent prognostic factor. In addition, we further found that these phagocytic regulators-related signatures were closely related to the immune microenvironment and immunotherapy in LUAD patients, and could well predict the efficacy of immunotherapy in patients. In vitro cell experiments and Immunohistochemistry of clinical tissues showed that the expressions of FURIN, KIF23, SASH3, GNPNAT1 and ITGAL in normal lung cells/tissues and LUAD cells/tissues were consistent with bioinformatics results, and 3 of them had significant differences.ConclusionOur study identified a novel PRs-related signature that has potential application value in predicting the prognosis of LUAD patients and predicting the efficacy of immunotherapy. This provides a new basis for the prognosis assessment of LUAD patients and provides a novel target for immunotherapy of LUAD patients. |
| first_indexed | 2024-04-11T23:36:31Z |
| format | Article |
| id | doaj.art-16937bad958347368f06889e7b82e9ac |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T23:36:31Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-16937bad958347368f06889e7b82e9ac2022-12-22T03:56:55ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.988332988332Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinomaJingyang Li0Qinyun Du1Jiayi Sun2Li Xiang3Shaohui Wang4State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaBackgroundLung adenocarcinoma (LUAD) is a malignant tumor that seriously affects the prognosis of patients. Tumor-associated macrophages (TAMs) play a vital role in the tumor microenvironment and can be used as a potential target for tumor therapy, and phagocytosis regulators (PRs) are particularly important in this process. However, the PRs-related signature that can predict the potential prognostic and immunotherapeutic value in patients with LUAD has not been discovered.MethodsIn this study, we mainly analyzed the effect of phagocytosis regulators on the prognosis of LUAD, and based on multiple screening analyses including differential analysis, univariate Cox analysis, and Lasso analysis, we constructed a prognostic risk model consisting of five genes. To verify the stability of the model, survival analysis and ROC curve verification were carried out through multiple data sets. In addition, we also combined many factors, such as immune infiltrating cells, clinical grouping characteristics, immune examination sites, pro-inflammatory factors, and other factors as well as in vitro cell experiments and clinical tissue samples for further validation analysis.ResultsAfter identifying 29 differentially expressed PRs in LUAD samples, we further constructed a prognostic model consisting of five prognostic signatures (FURIN, KIF23, SASH3, GNPNAT1, and ITGAL). Further survival analysis tests, ROC verification, as well as univariate and multivariate Cox regression analysis showed that the risk score of the model could well predict the prognosis of LUAD patients and could be used as an independent prognostic factor. In addition, we further found that these phagocytic regulators-related signatures were closely related to the immune microenvironment and immunotherapy in LUAD patients, and could well predict the efficacy of immunotherapy in patients. In vitro cell experiments and Immunohistochemistry of clinical tissues showed that the expressions of FURIN, KIF23, SASH3, GNPNAT1 and ITGAL in normal lung cells/tissues and LUAD cells/tissues were consistent with bioinformatics results, and 3 of them had significant differences.ConclusionOur study identified a novel PRs-related signature that has potential application value in predicting the prognosis of LUAD patients and predicting the efficacy of immunotherapy. This provides a new basis for the prognosis assessment of LUAD patients and provides a novel target for immunotherapy of LUAD patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.988332/fulllung adenocarcinomaphagocytosis regulatorsprognostic valueimmunotherapeutic valuerisk score |
| spellingShingle | Jingyang Li Qinyun Du Jiayi Sun Li Xiang Shaohui Wang Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma Frontiers in Oncology lung adenocarcinoma phagocytosis regulators prognostic value immunotherapeutic value risk score |
| title | Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma |
| title_full | Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma |
| title_fullStr | Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma |
| title_full_unstemmed | Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma |
| title_short | Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma |
| title_sort | identification and validation of a novel phagocytosis regulators related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma |
| topic | lung adenocarcinoma phagocytosis regulators prognostic value immunotherapeutic value risk score |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.988332/full |
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