Abstract
BackgroundGlioblastoma 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.ObjectiveWe sought to identify an efficient lymphocyte activation-associated gene signature that could predict the progression and prognosis of GBM.MethodsWe 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.ResultsWe 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.ConclusionsIn 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.
Highlights
Glioblastoma multiforme (GBM) as grade IV diffuse glioma, is one of the most aggressive and lethal brain cancers
We developed a lymphocyte activation-associated gene signature which can predict the overall survival of GBM patients in training data set and validated its prognostic value in another two independent cohorts
The transcriptional profile of GBM patients and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA)
Summary
Glioblastoma multiforme (GBM) as grade IV diffuse glioma, is one of the most aggressive and lethal brain cancers. IDH status is a classical marker of GBM, patients with IDH mutation are tend to have a better survival [3,4,5]. GBM patients can be divided into four distinct molecular subtypes based on gene expression profiling, including proneural, neural, classical and mesenchymal [6, 7]. The median overall survival of GBM patients is only 15 months, which suggested that the drug treatments might be ineffective for most of patients [9]. Glioblastoma multiforme (GBM) is the most aggressive primary central nervous system malignant tumor that has poor prognosis.
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