CRISPR-cas9 screening identified lethal genes enriched in Hippo kinase pathway and of predictive significance in primary low-grade glioma.

BACKGROUND: Low-grade gliomas (LGG) are a type of brain tumor that can be lethal, and it is essential to identify genes that are correlated with patient prognosis. In this study, we aimed to use CRISPR-cas9 screening data to identify key signaling pathways and develop a genetic signature associated with high-risk, low-grade glioma patients. METHODS: The study used CRISPR-cas9 screening data to identify essential genes correlated with cell survival in LGG. We used RNA-seq data to identify differentially expressed genes (DEGs) related to cell viability. Moreover, we used the least absolute shrinkage and selection operator (LASSO) method to construct a genetic signature for predicting overall survival in patients. We performed enrichment analysis to identify pathways mediated by DEGs, overlapping genes, and genes shared in the Weighted correlation network analysis (WGCNA). Finally, the study used western blot, qRT-PCR, and IHC to detect the expression of hub genes from signature in clinical samples. RESULTS: The study identified 145 overexpressed oncogenes in low-grade gliomas using the TCGA database. These genes were intersected with lethal genes identified in the CRISPR-cas9 screening data from Depmap database, which are enriched in Hippo pathways. A total of 19 genes were used to construct a genetic signature, and the Hippo signaling pathway was found to be the predominantly enriched pathway. The signature effectively distinguished between low- and high-risk patients, with high-risk patients showing a shorter overall survival duration. Differences in hub gene expression were found in different clinical samples, with the protein and mRNA expression of REP65 being significantly up-regulated in tumor cells. The study suggests that the Hippo signaling pathway may be a critical regulator of viability and tumor proliferation and therefore is an innovative new target for treating cancerous brain tumors, including low-grade gliomas. CONCLUSION: Our study identified a novel genetic signature associated with high-risk, LGG patients. We found that the Hippo signaling pathway was significantly enriched in this signature, indicating that it may be a critical regulator of tumor viability and proliferation in LGG. Targeting the Hippo pathway could be an innovative new strategy for treating LGG.

Abnormal Rhomboid Lip and Choroid Plexus Should be Valued in Microvascular Decompression for Vestibulocochlear Diseases.

BACKGROUND: Surgical outcomes for functional vestibulocochlear diseases vary, and the influencing factors are not fully understood. The role of a rhomboid lip (RL) and choroid plexus (CP) in microvascular decompression (MVD) of the vestibulocochlear nerve has not been studied. This study aims to evaluate the surgical efficacy of MVD for vestibulocochlear diseases, with and without addressing the RL and CP, to enhance our understanding of their etiology. METHODS: A total of 15 patients who underwent MVD for the vestibulocochlear nerve between 2013 and 2022 were retrospectively identified and followed up. The patients were classified into 4 categories: vestibular paroxysmia (VP), benign positional paroxysmal vertigo (BPPV), and Meniere disease (MD). The fourth was a "tinnitus" group. The relief of symptoms, recurrence, satisfaction after surgery, available relevant imaging studies, and intraoperative observation data were evaluated. RESULTS: Following MVD, 6 of the 7 patients in the VP group, the 1 patient in the BPPV group, and 1 of 2 patients in the MD group were completely relieved of vertigo. The seventh VP patient showed significant improvement. The 5 patients in the "tinnitus" group remained unchanged. Retrospectively, 4 patients from the VP, BPPV, and MD groups who underwent RL incision and CP excision were also free of vertigo, although vascular compression was not confirmed in these cases. CONCLUSIONS: MVD is generally considered a useful treatment for VP and could also be effective in managing recurrent vertigo caused by BPPV and MD. Our results highlight the potential role of an abnormal RL and CP in the development of vertigo symptoms. Patients presenting with "tinnitus" require further investigation and might not be suitable for MVD.