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

PeerJ. 2021 Aug 25;9:e12070. doi: 10.7717/peerj.12070. eCollection 2021.

Abstract

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.

Keywords: Glioblastoma multiforme (GBM); Lymphocyte activation-associated gene signature; Lymphocyte activity; Overall survival; Prognostic biomarker.

Grant support

This work was supported by the Heilongjiang Postdoctoral Foundation (Grant No. LBH-Z19082) and the Special funds for the construction of higher education in Heilongjiang Province (Grant No. UNPYSCT-2018068). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.