Gliomas are complex and heterogeneous central nervous system tumors with poor prognosis. Despite the increasing development of aggressive combination therapies, the prognosis of glioma is generally unsatisfactory. Exosomal microRNA (miRNA) has been successfully used in other diseases as a reliable biomarker and even therapeutic target. Recent studies show that exosomal miRNA plays an important role in glioma occurrence, development, invasion, metastasis, and treatment resistance. However, the association of exosomal miRNA between glioma has not been systemically characterized. This will provide a theoretical basis for us to further explore the relationship between exosomal miRNAs and glioma and also has a positive clinical significance in the innovative diagnosis and treatment of glioma.

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Autophagy is a highly conserved lysosomal degradation process essential in tumorigenesis. However, the involvement of autophagy-related lncRNA in low-grade gliomas (LGG) remains a pending question. Efforts were made to establish an autophagy-related lncRNA signature prognostic in LGG patients, and to explore the behind potential function. We used Univariate Cox, Least Absolute Shrinkage and Selection Operator (Lasso), and Multivariate Cox regression models were designed to establish an autophagy-related lncRNA prognostic signature. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve, nomogram, C-index, calibration curve and clinical decision-making curve were adopted to assess the predictive capability of the identified signature.A signature comprising 9 autophagy-related lncRNAs (AL136964.1, ARHGEF26-AS1, PCED1B-AS1, AS104072.1, PRKCQ-AS1, LINC00957, AS125616.1, PSMB8-AS1, and AC087741.1) was identified as a prognostic model. LGG patients were allocated into high- and low-risk cohorts depending on the median model-based Riskscore. The survival analysis showed a 10-year survival rate of 9.3% (95% CI: 1.91-45.3%) in high-risk LGG patients and 48.4% (95% CI: 24.7-95.0%) in low-risk individuals in the training set. While those of patients in the validation set were 13.48% (95% CI: 4.52-40.2%) for high-risk LGG patients and 48.4% (95% CI: 28.04-83.4%) for low-risk LGG patients, respectively. This suggested a relatively low survival in high-risk cases compared to low-risk individuals. In addition, LncRNA signature was independently prognostic and potentially associated with the progression of LGG. Taken together, our constructed 9 autophagy-related lncRNA signature may play a crucial part in the diagnosis and treatment for LGG, which may guide to open up a new avenues for tumor targeted therapy.

Background: Gliomas are complex and heterogeneous central nervous system tumors, with Low-grade Glioma (LGG)as the most common pathological type. But studies on the predictive effect of a single gene on LGG are limited. VASH1 is an epigenetic regulator with various tumors. However, the role of VASH1 in LGG remains confused. This is the first research focusing on the prognostic value and underlying mechanism of VASH1 in LGG.Methods: In this research, three independent datasets were used for mRNA-related analysis: two datasets from the TCGA and CGGA (CGGA-mRNA seq 693 and CGGA-mRNA seq 325). We analyzed and screened the clinical significance of VASH1 in overall survival and DSS of various cancers. TIMER and CIBERSORT algorithms were employed to investigate the effect of VASH1 on the tumor microenvironment. GSEA along with GO and KEGG enrichment analyses were conducted to uncover the biological functions of VASH1. In addition, a LGG patient cohort (The First Affiliated Hospital of Xinjiang Medical University) was utilized for analysis of cell infiltration by immunohistochemical, Western-blot, and qPCR; then to verify its function in regulating LGG progression in vitro.Result: In this study, the results of generalized cancer survival analysis showed that abnormal VASH1 expression was associated with poor prognosis (overall survival (OS) and disease-specific survival (DSS) in patients with adrenal cortical carcinoma (ACC), low-grade glioma (LGG), pancreatic adenocarcinoma (PAAD) and hepatocellular carcinoma (LIHC) (P<0.05). Meanwhile, VASH1 was correlated with the immune invasion, immune score, immune checkpoint, and TBM of the above four tumors, and the correlation between VASH1 expression and LGG was the strongest. In addition, we found that VASH1-mediated changes in gene expression are closely related to cell cycle, P53, Notch, and TGF-β signaling pathways. In addition, immunostaining and RT-PCR were performed on our cohort, and the results showed that VASH1 expression was significantly higher than that of para-cancer tissues (P<0.05). Kaplan-Meier survival analysis results showed that VASH1 was associated with shorter survival (OS) and shorter DFS in high-risk LGG patients (P<0.05). Multivariate Cox analysis showed that high VASH1 expression was an independent risk factor for the prognosis of LGG patients (HR=1.65, P=0.02). Finally, a high level of VASH1 was found in U-251 cell lines by in vitro cell experiments, and the migration and invasion ability of U-251 cells were significantly improved after knockdown of VASH1 (P<0.01), which further confirmed the function of VASH1.Conclusion: In conclusion, this study preliminarily indicates that VASH1 can be used as a prognostic biomarker and potential therapeutic target for LGG, and has important clinical application value.

Background. VASH1 is a novel angiogenic regulatory factor, that participates in the process of carcinogenesis and the development of diverse tumors. Our study aimed to investigate the expression and prognostic value of the VASH1 in Lower-Grade Glioma (LGG), to explore its functional network in LGG and its effects on biological behaviors. Methods. LGG transcriptome data, somatic mutation profiles and clinical features analyzed in the present study were obtained from the TCGA, GTEx, CCLE, CGGA, UALCAN, and GEPIA2 databases, as well as clinical data and tissue sections of 83 LGG patients in our hospital. The expression characteristics of VASH1 in LGG were investigated by univariate, multivariate, immunohistochemistry, qRT-PCR, and western-blot. Subsequently, we analyzed the prognostic significance of VASH1 in LGG patients by survival analysis, subject operation characteristic curve, correlation analysis, external validation, independent prognostic significance analysis, and clinical stratification, and confirmed its biological effect on glioma cell lines in vitro. Finally, we performed GO, KEGG, and GSEA to clarify biological functions and related pathways. CIBERSORT and ESTIMATE algorithms were used to calculate the proportion of immune cells and immune microenvironment fraction in LGG. Result. We found that VASH1 is highly expressed in LGG tissues and is associated with poor prognosis, WHO grade, IDH1 wild-type, and progressive disease ( P < 0.05 ). Multivariate and the Nomogram model showed that high VASH1 expression was an independent risk factor for glioma prognosis and had better prognostic prediction efficacy in different LGG Patient cohorts (HR = 4.753 and P = 0.002 ). In vitro experiments showed that knockdown of VASH1 expression in glioma cell lines caused increased glioma cell proliferation, invasion, and migration capacity. The mechanism may be related to VASH1 promoting microtubule formation and remodeling of immune microenvironment. Conclusion. Our study firstly found that high VASH1 expression was associated with poor prognosis. In addition, We identified the possible mechanism by which VASH1 functioned in LGG. VASH1 inhibits the invasion and migration of tumor cells by affecting microtubule formation and immune infiltration in the tumor microenvironment. May be an important endogenous anti-tumor factor for LGG and provide a potential biomarker for individualized treatment of LGG.