Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysis

Background Glioblastoma multiforme (GBM) is a highly, malignant tumor of the primary central nervous system. Patients diagnosed with this type of tumor have a poor prognosis. Lymphocyte activation plays important roles in the development of cancers and its therapeutic treatments. Objective We sought...

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Main Authors: Yujia Lan, Erjie Zhao, Xinxin Zhang, Xiaojing Zhu, Linyun Wan, Suru A, Yanyan Ping, Yihan Wang
Format: Article
Language:English
Published: PeerJ Inc. 2021-08-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/12070.pdf
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author Yujia Lan
Erjie Zhao
Xinxin Zhang
Xiaojing Zhu
Linyun Wan
Suru A
Yanyan Ping
Yihan Wang
author_facet Yujia Lan
Erjie Zhao
Xinxin Zhang
Xiaojing Zhu
Linyun Wan
Suru A
Yanyan Ping
Yihan Wang
author_sort Yujia Lan
collection DOAJ
description Background Glioblastoma multiforme (GBM) is a highly, malignant tumor of the primary central nervous system. Patients diagnosed with this type of tumor have a poor prognosis. Lymphocyte activation plays important roles in the development of cancers and its therapeutic treatments. Objective We sought to identify an efficient lymphocyte activation-associated gene signature that could predict the progression and prognosis of GBM. Methods We used univariate Cox proportional hazards regression and stepwise regression algorithm to develop a lymphocyte activation-associated gene signature in the training dataset (TCGA, n = 525). Then, the signature was validated in two datasets, including GSE16011 (n = 150) and GSE13041 (n = 191) using the Kaplan Meier method. Univariate and multivariate Cox proportional hazards regression models were used to adjust for clinicopathological factors. Results We identified a lymphocyte activation-associated gene signature (TCF3, IGFBP2, TYRO3 and NOD2) in the training dataset and classified the patients into high-risk and low-risk groups with significant differences in overall survival (median survival 15.33 months vs 12.57 months, HR = 1.55, 95% CI [1.28–1.87], log-rank test P < 0.001). This signature showed similar prognostic values in the other two datasets. Further, univariate and multivariate Cox proportional hazards regression models analysis indicated that the signature was an independent prognostic factor for GBM patients. Moreover, we determined that there were differences in lymphocyte activity between the high- and low-risk groups of GBM patients among all datasets. Furthermore, the lymphocyte activation-associated gene signature could significantly predict the survival of patients with certain features, including IDH-wildtype patients and patients undergoing radiotherapy. In addition, the signature may also improve the prognostic power of age. Conclusions In summary, our results suggested that the lymphocyte activation-associated gene signature is a promising factor for the survival of patients, which is helpful for the prognosis of GBM patients.
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spelling doaj.art-403a72d00d7747d8bd5f75ebf2f45d2c2023-12-03T10:25:58ZengPeerJ Inc.PeerJ2167-83592021-08-019e1207010.7717/peerj.12070Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysisYujia Lan0Erjie Zhao1Xinxin Zhang2Xiaojing Zhu3Linyun Wan4Suru A5Yanyan Ping6Yihan Wang7Harbin Medical University, College of Bioinformatics Science and Technology, Harbin, ChinaHarbin Medical University, College of Bioinformatics Science and Technology, Harbin, ChinaHarbin Medical University, College of Bioinformatics Science and Technology, Harbin, ChinaHarbin Medical University, College of Bioinformatics Science and Technology, Harbin, ChinaHarbin Medical University, College of Bioinformatics Science and Technology, Harbin, ChinaHarbin Medical University, College of Bioinformatics Science and Technology, Harbin, ChinaHarbin Medical University, College of Bioinformatics Science and Technology, Harbin, ChinaHarbin Medical University, College of Bioinformatics Science and Technology, Harbin, ChinaBackground Glioblastoma multiforme (GBM) is a highly, malignant tumor of the primary central nervous system. Patients diagnosed with this type of tumor have a poor prognosis. Lymphocyte activation plays important roles in the development of cancers and its therapeutic treatments. Objective We sought to identify an efficient lymphocyte activation-associated gene signature that could predict the progression and prognosis of GBM. Methods We used univariate Cox proportional hazards regression and stepwise regression algorithm to develop a lymphocyte activation-associated gene signature in the training dataset (TCGA, n = 525). Then, the signature was validated in two datasets, including GSE16011 (n = 150) and GSE13041 (n = 191) using the Kaplan Meier method. Univariate and multivariate Cox proportional hazards regression models were used to adjust for clinicopathological factors. Results We identified a lymphocyte activation-associated gene signature (TCF3, IGFBP2, TYRO3 and NOD2) in the training dataset and classified the patients into high-risk and low-risk groups with significant differences in overall survival (median survival 15.33 months vs 12.57 months, HR = 1.55, 95% CI [1.28–1.87], log-rank test P < 0.001). This signature showed similar prognostic values in the other two datasets. Further, univariate and multivariate Cox proportional hazards regression models analysis indicated that the signature was an independent prognostic factor for GBM patients. Moreover, we determined that there were differences in lymphocyte activity between the high- and low-risk groups of GBM patients among all datasets. Furthermore, the lymphocyte activation-associated gene signature could significantly predict the survival of patients with certain features, including IDH-wildtype patients and patients undergoing radiotherapy. In addition, the signature may also improve the prognostic power of age. Conclusions In summary, our results suggested that the lymphocyte activation-associated gene signature is a promising factor for the survival of patients, which is helpful for the prognosis of GBM patients.https://peerj.com/articles/12070.pdfLymphocyte activation-associated gene signatureGlioblastoma multiforme (GBM)Prognostic biomarkerLymphocyte activityOverall survival
spellingShingle Yujia Lan
Erjie Zhao
Xinxin Zhang
Xiaojing Zhu
Linyun Wan
Suru A
Yanyan Ping
Yihan Wang
Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysis
PeerJ
Lymphocyte activation-associated gene signature
Glioblastoma multiforme (GBM)
Prognostic biomarker
Lymphocyte activity
Overall survival
title Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysis
title_full Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysis
title_fullStr Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysis
title_full_unstemmed Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysis
title_short Prognostic impact of a lymphocyte activation-associated gene signature in GBM based on transcriptome analysis
title_sort prognostic impact of a lymphocyte activation associated gene signature in gbm based on transcriptome analysis
topic Lymphocyte activation-associated gene signature
Glioblastoma multiforme (GBM)
Prognostic biomarker
Lymphocyte activity
Overall survival
url https://peerj.com/articles/12070.pdf
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