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N1-methyladenosine (m1A) modification is a crucial post-transcriptional regulatory mechanism of messenger RNA (mRNA) in living organisms. Few studies have focused on analysis of m1A regulators in lower-grade gliomas (LGG). We employed the Nonnegative Matrix Factorization (NMF) technique on The Cancer Genome Atlas (TCGA) dataset to categorize LGG patients into 2 groups. These groups exhibited substantial disparities in terms of both overall survival (OS) and levels of infiltrating immune cells. We collected the significantly differentially expressed immune-related genes between the 2 clusters, and performed LASSO regression analysis to obtain m1AScores, and established an m1A-related immune-related gene signature (m1A-RIGS). Next, we categorized all patients with LGG into high- and low-risk subgroups, predictive significance of m1AScore was confirmed by conducting univariate/multivariate Cox regression analyses. Additionally, we confirmed variations in immune-related cells and ssGSEA and among the high-/low-risk subcategories in the TCGA dataset. Finally, our study characterized the effects of MSR1 and BIRC5 on LGG cells utilizing Edu assay and flow cytometry to explore the effects of modulation of these genes on glioma. The results of this study suggested that m1A-RIGS may be an excellent prognostic indicator for patients with LGG, and could also promote development of novel immune-based treatment strategies for LGG. Additionally, BIRC5 and MSR1 may be potential therapeutic targets for LGG.

Abstract Background The p21-activated kinase (PAK) family (PAKs) plays a key role in the formation and development of human tumors. However, a systematic analysis of PAKs in human cancers is lacking and the potential role of PAKs in cancer immunity has not been explored. Methods We used datasets from in The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression database (GTEx). Results Based on TCGA datasets most PAKs show noteworthy differences in expression between tumors and corresponding normal tissues or across different tumor tissues. Patients with high expression of PAKs often show a worse prognosis. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. Further analysis showed that the impact of PAKs on immunity varies with the type of tumor and the respective tumor microenvironment. PAK1 and PAK4 may be stronger predictors of immune characteristics, and are more suitable as drugs and molecular therapeutic targets. Furthermore, Cox regression analysis revealed that a PAK gene signature could be used as an independent prognostic factor for lower grade glioma (LGG) and glioblastoma (GBM). Gene set enrichment analysis (GSEA) analysis indicated that PAK genes may affect the occurrence and development of GBM through the PI3K signaling pathway. Further experiments verified that PAK1 and AKT1 have a significant interaction in GBM cells, and inhibiting the overactivation of PAK1 can significantly inhibit the proliferation of GBM cells. Conclusions Our study provides a rationale for further research on the prognostic and therapeutic potential of PAKs in human tumors.

Diffuse gliomas are the most common malignant brain tumors with the highest mortality and recurrence rate in adults. Integrin alpha-2 (ITGA2) is involved in a series of biological processes, including cell adhesion, stemness regulation, angiogenesis, and immune/blood cell functions. The role of ITGA2 in lower-grade gliomas (LGGs) is not well defined. Firstly, we downloaded RNA sequencing and relevant clinical information from The Cancer Genome Atlas cohort, the Chinese Glioma Genome Atlas cohort, and related immune cohorts. Next, prognosis analysis, difference analysis, clinical model construction, enrichment analysis, and immune infiltration analysis are performed for this study. These analyses indicated that ITGA2 may have clinical application value and research value in LGG immunotherapy. We also detected the mRNA and protein expression of ITGA2 in three LGG cell lines and normal glial cells using quantitative real-time polymerase chain reaction assay and western blot assay. Our study not only offers a novel target for LGG immunotherapy but also can better comprehend the mechanism of the development and progression of patients with LGG. This study revealed that ITGA2 may be a potential prognostic and predictive biomarker for LGG, which can bring new insights into targeted immunotherapy.