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.
ABSTRACT
Our previous studies have shown that cancer mortality in high background-radiation areas of China was lower than that in a control area, indicating the possibility of an adaptive response in high background-radiation areas. Our aim is to determine the effect of low-dose radiation on the level of DNA oxidative damage, DNA damage repair, antioxidant capacity, and apoptosis in high background-radiation area and control area populations of Guangdong through a molecular epidemiological study in order to identify adaptive response. Blood samples were collected from male residents aged 50 to 59 y in a high background-radiation area (Yangjiang) and a control area (Enping), and activities of superoxide dismutase, glutathione, catalase, total antioxidant capacity, and expression of O6-methylguanine-DNA methyltransferase gene (MGMT), human 8-oxoguanine DNA N-glycosylase 1 gene (hOGG1), proapoptotic genes and antiapoptotic genes, oxidative-stress-related genes, as well as concentrations of 8-OHdG, TrxR, HSP27, and MT-COX2 were determined. The activities of antioxidative enzymes, relative mRNA expression level of DNA repair genes, antiapoptotic genes, oxidative-stress-related genes HSPB1 and MT-COX2, and the concentration of antioxidant index TrxR in the high background-radiation area population increased significantly compared to the control population (p < 0.05). The relative mRNA expression level of proapoptotic genes and the concentration of DNA oxidative damage index 8-OHdG were significantly lower in the high background-radiation area compared to those in the control area (p < 0.05). In conclusion, under long-term, natural, high background, ionizing radiation, DNA damage-repair capacity and antioxidant capacity of inhabitants in the high background-radiation area may be enhanced. Additionally, it could induce up regulation of cell-survival gene expression and down regulation of apoptotic gene expression. It might be speculated that enhanced antioxidant and DNA repair capacity and inhibition of apoptosis might play important roles in adaptive response of low-dose radiation in high background-radiation areas.
