Construction and validation of a robust prognostic model based on immune features in sepsis
PurposeSepsis, with life-threatening organ failure, is caused by the uncontrolled host response to infection. Immune response plays an important role in the pathophysiology of sepsis. Immune-related genes (IRGs) are promising novel biomarkers that have been used to construct the diagnostic and progn...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.994295/full |
| _version_ | 1811160459961696256 |
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| author | Yongxin Zheng Yongxin Zheng Baiyun Liu Baiyun Liu Xiumei Deng Xiumei Deng Yubiao Chen Yubiao Chen Yongbo Huang Yongbo Huang Yu Zhang Yu Zhang Yonghao Xu Yonghao Xu Ling Sang Ling Sang Xiaoqing Liu Xiaoqing Liu Yimin Li Yimin Li |
| author_facet | Yongxin Zheng Yongxin Zheng Baiyun Liu Baiyun Liu Xiumei Deng Xiumei Deng Yubiao Chen Yubiao Chen Yongbo Huang Yongbo Huang Yu Zhang Yu Zhang Yonghao Xu Yonghao Xu Ling Sang Ling Sang Xiaoqing Liu Xiaoqing Liu Yimin Li Yimin Li |
| author_sort | Yongxin Zheng |
| collection | DOAJ |
| description | PurposeSepsis, with life-threatening organ failure, is caused by the uncontrolled host response to infection. Immune response plays an important role in the pathophysiology of sepsis. Immune-related genes (IRGs) are promising novel biomarkers that have been used to construct the diagnostic and prognostic model. However, an IRG prognostic model used to predict the 28-day mortality in sepsis was still limited. Therefore, the study aimed to develop a prognostic model based on IRGs to identify patients with high risk and predict the 28-day mortality in sepsis. Then, we further explore the circulating immune cell and immunosuppression state in sepsis.Materials and methodsThe differentially expressed genes (DEGs), differentially expressed immune-related genes (DEIRGs), and differentially expressed transcription factors (DETFs) were obtained from the GEO, ImmPort, and Cistrome databases. Then, the TFs-DEIRGs regulatory network and prognostic prediction model were constructed by Cox regression analysis and Pearson correlation analysis. The external datasets also validated the reliability of the prognostic model. Based on the prognostic DEIRGs, we developed a nomogram and conducted an independent prognosis analysis to explore the relationship between DEIRGs in the prognostic model and clinical features in sepsis. Besides, we further evaluate the circulating immune cells state in sepsis.ResultsA total of seven datasets were included in our study. Among them, GSE65682 was identified as a discovery cohort. The results of GSEA showed that there is a significant correlation between sepsis and immune response. Then, based on a P value <0.01, 69 prognostic DEIRGs were obtained and the potential molecular mechanisms of DEIRGs were also clarified. According to multivariate Cox regression analysis, 22 DEIRGs were further identified to construct the prognostic model and identify patients with high risk. The Kaplan–Meier survival analysis showed that high-risk groups have higher 28-day mortality than low-risk groups (P=1.105e-13). The AUC value was 0.879 which symbolized that the prognostic model had a better accuracy to predict the 28-day mortality. The external datasets also prove that the prognostic model had an excellent prediction value. Furthermore, the results of correlation analysis showed that patients with Mars1 might have higher risk scores than Mars2-4 (P=0.002). According to the previous study, Mars1 endotype was characterized by immunoparalysis. Thus, the sepsis patients in high-risk groups might exist the immunosuppression. Between the high-risk and low-risk groups, circulating immune cells types were significantly different, and risk score was significantly negatively correlated with naive CD4+ T cells (P=0.019), activated NK cells (P=0.0045), monocytes (P=0.0134), and M1 macrophages (P=0.0002).ConclusionsOur study provides a robust prognostic model based on 22 DEIRGs which can predict 28-day mortality and immunosuppression status in sepsis. The higher risk score was positively associated with 28-day mortality and the development of immunosuppression. IRGs are a promising biomarker that might facilitate personalized treatments for sepsis. |
| first_indexed | 2024-04-10T05:57:38Z |
| format | Article |
| id | doaj.art-c15eb30f17f04798b1709e3bd53ca599 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T05:57:38Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c15eb30f17f04798b1709e3bd53ca5992023-03-03T10:11:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.994295994295Construction and validation of a robust prognostic model based on immune features in sepsisYongxin Zheng0Yongxin Zheng1Baiyun Liu2Baiyun Liu3Xiumei Deng4Xiumei Deng5Yubiao Chen6Yubiao Chen7Yongbo Huang8Yongbo Huang9Yu Zhang10Yu Zhang11Yonghao Xu12Yonghao Xu13Ling Sang14Ling Sang15Xiaoqing Liu16Xiaoqing Liu17Yimin Li18Yimin Li19State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaPurposeSepsis, with life-threatening organ failure, is caused by the uncontrolled host response to infection. Immune response plays an important role in the pathophysiology of sepsis. Immune-related genes (IRGs) are promising novel biomarkers that have been used to construct the diagnostic and prognostic model. However, an IRG prognostic model used to predict the 28-day mortality in sepsis was still limited. Therefore, the study aimed to develop a prognostic model based on IRGs to identify patients with high risk and predict the 28-day mortality in sepsis. Then, we further explore the circulating immune cell and immunosuppression state in sepsis.Materials and methodsThe differentially expressed genes (DEGs), differentially expressed immune-related genes (DEIRGs), and differentially expressed transcription factors (DETFs) were obtained from the GEO, ImmPort, and Cistrome databases. Then, the TFs-DEIRGs regulatory network and prognostic prediction model were constructed by Cox regression analysis and Pearson correlation analysis. The external datasets also validated the reliability of the prognostic model. Based on the prognostic DEIRGs, we developed a nomogram and conducted an independent prognosis analysis to explore the relationship between DEIRGs in the prognostic model and clinical features in sepsis. Besides, we further evaluate the circulating immune cells state in sepsis.ResultsA total of seven datasets were included in our study. Among them, GSE65682 was identified as a discovery cohort. The results of GSEA showed that there is a significant correlation between sepsis and immune response. Then, based on a P value <0.01, 69 prognostic DEIRGs were obtained and the potential molecular mechanisms of DEIRGs were also clarified. According to multivariate Cox regression analysis, 22 DEIRGs were further identified to construct the prognostic model and identify patients with high risk. The Kaplan–Meier survival analysis showed that high-risk groups have higher 28-day mortality than low-risk groups (P=1.105e-13). The AUC value was 0.879 which symbolized that the prognostic model had a better accuracy to predict the 28-day mortality. The external datasets also prove that the prognostic model had an excellent prediction value. Furthermore, the results of correlation analysis showed that patients with Mars1 might have higher risk scores than Mars2-4 (P=0.002). According to the previous study, Mars1 endotype was characterized by immunoparalysis. Thus, the sepsis patients in high-risk groups might exist the immunosuppression. Between the high-risk and low-risk groups, circulating immune cells types were significantly different, and risk score was significantly negatively correlated with naive CD4+ T cells (P=0.019), activated NK cells (P=0.0045), monocytes (P=0.0134), and M1 macrophages (P=0.0002).ConclusionsOur study provides a robust prognostic model based on 22 DEIRGs which can predict 28-day mortality and immunosuppression status in sepsis. The higher risk score was positively associated with 28-day mortality and the development of immunosuppression. IRGs are a promising biomarker that might facilitate personalized treatments for sepsis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.994295/fullsepsisimmuneprognostic model28-day mortalityimmunosuppression |
| spellingShingle | Yongxin Zheng Yongxin Zheng Baiyun Liu Baiyun Liu Xiumei Deng Xiumei Deng Yubiao Chen Yubiao Chen Yongbo Huang Yongbo Huang Yu Zhang Yu Zhang Yonghao Xu Yonghao Xu Ling Sang Ling Sang Xiaoqing Liu Xiaoqing Liu Yimin Li Yimin Li Construction and validation of a robust prognostic model based on immune features in sepsis Frontiers in Immunology sepsis immune prognostic model 28-day mortality immunosuppression |
| title | Construction and validation of a robust prognostic model based on immune features in sepsis |
| title_full | Construction and validation of a robust prognostic model based on immune features in sepsis |
| title_fullStr | Construction and validation of a robust prognostic model based on immune features in sepsis |
| title_full_unstemmed | Construction and validation of a robust prognostic model based on immune features in sepsis |
| title_short | Construction and validation of a robust prognostic model based on immune features in sepsis |
| title_sort | construction and validation of a robust prognostic model based on immune features in sepsis |
| topic | sepsis immune prognostic model 28-day mortality immunosuppression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.994295/full |
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