Comprehensive Analysis to Identify the Vasohibin1 (VASH1) Emerges as a Novel Prognosis Biomarker in High-Risk Low-Grade Glioma

Abstract

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.

Identification of VASH1 as a Potential Prognostic Biomarker of Lower-Grade Glioma by Quantitative Proteomics and Experimental Verification

“…The manuscript has been submitted as a preprint in the below link [ 36 ]: https://www.researchsquare.com/article/rs-1167387/v1…”