Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma

Abstract Background The incidence of stage I and stage II lung adenocarcinoma (LUAD) is likely to increase with the introduction of annual screening programs for high-risk individuals. We aimed to identify a reliable prognostic signature with immune-related genes that can predict prognosis and help...

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Main Authors: Pancheng Wu, Yi Zheng, Yanyu Wang, Yadong Wang, Naixin Liang
Format: Article
Language:English
Published: BMC 2020-10-01
Series:Journal of Translational Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12967-020-02545-z
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spelling doaj-3b436ae1644d4343b550a91fafa4729f2020-11-25T04:09:18ZengBMCJournal of Translational Medicine1479-58762020-10-0118111210.1186/s12967-020-02545-zDevelopment and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinomaPancheng Wu0Yi Zheng1Yanyu Wang2Yadong Wang3Naixin Liang4Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical SciencesAbstract Background The incidence of stage I and stage II lung adenocarcinoma (LUAD) is likely to increase with the introduction of annual screening programs for high-risk individuals. We aimed to identify a reliable prognostic signature with immune-related genes that can predict prognosis and help making individualized management for patients with early-stage LUAD. Methods The public LUAD cohorts were obtained from the large-scale databases including 4 microarray data sets from the Gene Expression Omnibus (GEO) and 1 RNA-seq data set from The Cancer Genome Atlas (TCGA) LUAD cohort. Only early-stage patients with clinical information were included. Cox proportional hazards regression model was performed to identify the candidate prognostic genes in GSE30219, GSE31210 and GSE50081 (training set). The prognostic signature was developed using the overlapped prognostic genes based on a risk score method. Kaplan–Meier curve with log-rank test and time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic value and performance of this signature, respectively. Furthermore, the robustness of this prognostic signature was further validated in TCGA-LUAD and GSE72094 cohorts. Results A prognostic immune signature consisting of 21 immune-related genes was constructed using the training set. The prognostic signature significantly stratified patients into high- and low-risk groups in terms of overall survival (OS) in training data set, including GSE30219 (HR = 4.31, 95% CI 2.29–8.11; P = 6.16E−06), GSE31210 (HR = 11.91, 95% CI 4.15–34.19; P = 4.10E−06), GSE50081 (HR = 3.63, 95% CI 1.90–6.95; P = 9.95E−05), the combined data set (HR = 3.15, 95% CI 1.98–5.02; P = 1.26E−06) and the validation data set, including TCGA-LUAD (HR = 2.16, 95% CI 1.49–3.13; P = 4.54E−05) and GSE72094 (HR = 2.95, 95% CI 1.86–4.70; P = 4.79E−06). Multivariate cox regression analysis demonstrated that the 21-gene signature could serve as an independent prognostic factor for OS after adjusting for other clinical factors. ROC curves revealed that the immune signature achieved good performance in predicting OS for early-stage LUAD. Several biological processes, including regulation of immune effector process, were enriched in the immune signature. Moreover, the combination of the signature with tumor stage showed more precise classification for prognosis prediction and treatment design. Conclusions Our study proposed a robust immune-related prognostic signature for estimating overall survival in early-stage LUAD, which may be contributed to make more accurate survival risk stratification and individualized clinical management for patients with early-stage LUAD.http://link.springer.com/article/10.1186/s12967-020-02545-zLung adenocarcinomaOverall survivalImmune-related genesPrognosisRisk score
collection DOAJ
language English
format Article
sources DOAJ
author Pancheng Wu
Yi Zheng
Yanyu Wang
Yadong Wang
Naixin Liang
spellingShingle Pancheng Wu
Yi Zheng
Yanyu Wang
Yadong Wang
Naixin Liang
Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma
Journal of Translational Medicine
Lung adenocarcinoma
Overall survival
Immune-related genes
Prognosis
Risk score
author_facet Pancheng Wu
Yi Zheng
Yanyu Wang
Yadong Wang
Naixin Liang
author_sort Pancheng Wu
title Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma
title_short Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma
title_full Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma
title_fullStr Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma
title_full_unstemmed Development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma
title_sort development and validation of a robust immune-related prognostic signature in early-stage lung adenocarcinoma
publisher BMC
series Journal of Translational Medicine
issn 1479-5876
publishDate 2020-10-01
description Abstract Background The incidence of stage I and stage II lung adenocarcinoma (LUAD) is likely to increase with the introduction of annual screening programs for high-risk individuals. We aimed to identify a reliable prognostic signature with immune-related genes that can predict prognosis and help making individualized management for patients with early-stage LUAD. Methods The public LUAD cohorts were obtained from the large-scale databases including 4 microarray data sets from the Gene Expression Omnibus (GEO) and 1 RNA-seq data set from The Cancer Genome Atlas (TCGA) LUAD cohort. Only early-stage patients with clinical information were included. Cox proportional hazards regression model was performed to identify the candidate prognostic genes in GSE30219, GSE31210 and GSE50081 (training set). The prognostic signature was developed using the overlapped prognostic genes based on a risk score method. Kaplan–Meier curve with log-rank test and time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic value and performance of this signature, respectively. Furthermore, the robustness of this prognostic signature was further validated in TCGA-LUAD and GSE72094 cohorts. Results A prognostic immune signature consisting of 21 immune-related genes was constructed using the training set. The prognostic signature significantly stratified patients into high- and low-risk groups in terms of overall survival (OS) in training data set, including GSE30219 (HR = 4.31, 95% CI 2.29–8.11; P = 6.16E−06), GSE31210 (HR = 11.91, 95% CI 4.15–34.19; P = 4.10E−06), GSE50081 (HR = 3.63, 95% CI 1.90–6.95; P = 9.95E−05), the combined data set (HR = 3.15, 95% CI 1.98–5.02; P = 1.26E−06) and the validation data set, including TCGA-LUAD (HR = 2.16, 95% CI 1.49–3.13; P = 4.54E−05) and GSE72094 (HR = 2.95, 95% CI 1.86–4.70; P = 4.79E−06). Multivariate cox regression analysis demonstrated that the 21-gene signature could serve as an independent prognostic factor for OS after adjusting for other clinical factors. ROC curves revealed that the immune signature achieved good performance in predicting OS for early-stage LUAD. Several biological processes, including regulation of immune effector process, were enriched in the immune signature. Moreover, the combination of the signature with tumor stage showed more precise classification for prognosis prediction and treatment design. Conclusions Our study proposed a robust immune-related prognostic signature for estimating overall survival in early-stage LUAD, which may be contributed to make more accurate survival risk stratification and individualized clinical management for patients with early-stage LUAD.
topic Lung adenocarcinoma
Overall survival
Immune-related genes
Prognosis
Risk score
url http://link.springer.com/article/10.1186/s12967-020-02545-z
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AT yanyuwang developmentandvalidationofarobustimmunerelatedprognosticsignatureinearlystagelungadenocarcinoma
AT yadongwang developmentandvalidationofarobustimmunerelatedprognosticsignatureinearlystagelungadenocarcinoma
AT naixinliang developmentandvalidationofarobustimmunerelatedprognosticsignatureinearlystagelungadenocarcinoma
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