A Novel Six Autophagy-Related Genes Signature Associated With Outcomes and Immune Microenvironment in Lower-Grade Glioma

Abstract

Since autophagy and the immune microenvironment are deeply involved in the tumor development and progression of Lower-grade gliomas (LGG), our study aimed to construct an autophagy-related risk model for prognosis prediction and investigate the relationship between the immune microenvironment and risk signature in LGG. Therefore, we identified six autophagy-related genes (BAG1, PTK6, EEF2, PEA15, ITGA6, and MAP1LC3C) to build in the training cohort (n = 305 patients) and verify the prognostic model in the validation cohort (n = 128) and the whole cohort (n = 433), based on the data from The Cancer Genome Atlas (TCGA). The six-gene risk signature could divide LGG patients into high- and low-risk groups with distinct overall survival in multiple cohorts (all p < 0.001). The prognostic effect was assessed by area under the time-dependent ROC (t-ROC) analysis in the training, validation, and whole cohorts, in which the AUC value at the survival time of 5 years was 0.837, 0.755, and 0.803, respectively. Cox regression analysis demonstrated that the risk model was an independent risk predictor of OS (HR > 1, p < 0.05). A nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its robust predictive capacity. KM analysis revealed a significant difference in the subgroup analyses’ survival. Functional enrichment analysis revealed that these autophagy-related signatures were mainly involved in the phagosome and immune-related pathways. Besides, we also found significant differences in immune cell infiltration and immunotherapy targets between risk groups. In conclusion, we built a powerful predictive signature and explored immune components (including immune cells and emerging immunotherapy targets) in LGG.

A Bioinformatics-Based Analysis of an Anoikis-Related Gene Signature Predicts the Prognosis of Patients with Low-Grade Gliomas

“…BAG1 is a multifunctional protein associated with a variety of cellular processes, such as apoptosis, proliferation, growth, and motility [ 40 ]. As an autophagy-related gene, BAG1 is also considered to be an important prognostic factor in low-grade gliomas [ 41 ]. In colon cancer, knockdown of the neurotrophic factor BDNF suppresses the expression of the mesenchymal marker CDH2 leading to anoikis and immune resistance in tumor cells [ 42 ].…”

New insights into glioma frequency maps: From genetic and transcriptomic correlate to survival prediction

“…Conventional prediction models are usually based on clinical and molecular information 39 . In recent studies, gene signature, immune infiltration or other feature sets were also incorporated when building the prediction model 40 . However, all these predictors are limited by the availability of glioma samples.…”

A Novel Anoikis-Related Gene Signature Predicts Prognosis in Patients with Low-Grade Glioma and Reveals Immune Infiltration

“…While BAG1 is a multifunctional protein associated with a variety of cellular processes, such as apoptosis, proliferation, growth, and motility [38]. As an autophagy-related gene, BAG1 is also considered to be an important prognostic factor in low-grade gliomas [39]. In colon cancer, knockdown of the neurotrophic factor BDNF suppresses the expression of the mesenchymal marker CDH2 leading to anoikis and immune resistance in tumor cells [40].…”