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Expression of PKMYT1 in glioma and its association with prognosis, drug sensitivity, and immune infiltration
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Abstract:
[Abstract] Objective: To analyze by bioinformatics the association between the expression of membrane-associated tyrosine/threonine protein kinase 1 (PKMYT1) in glioma with its prognostic value, biological function, drug sensitivity, gene mutation, and immune infiltration. Methods: The differential expression of PKMYT1 was analyzed based on the Chinese Glioma Genome Atlas database (CGGA) and the Cancer Genome Atlas database (TCGA). Pathways likely to be enriched for PKMYT1 were predicted by gene ontology analysis (GO) and gene set enrichment analysis (GSEA). PKMYT1 was subjected to Pearson correlation and gene set variation analysis (GSVA) with cell cycle-related genes and gene sets. The survival prognosis, gene mutation, drug sensitivity and immune infiltration were further analyzed for PKMYT1 high and low expression groups of glioma patients. Results: PKMYT1 was significantly highly expressed in WHO high-grade glioma (P < 0.000 1), IDH wild-type glioma (P < 0.05), and glioblastoma (P < 0.000 1). Overall survival (OS) of patients in the PKMYT1 low expression group was significantly higher than that of the high expression group (P < 0.05). Cox regression analysis showed that PKMYT1 expression level was an independent prognostic factor for OS (P < 0.05). GO and GSEA analyses showed that the gene sets co-expressed with PKMYT1 were mainly enriched in signaling pathways such as cell cycle, DNA replication and DNA damage repair. Pearson correlation and GSVA analyses showed that the expression of PKMYT1 was significantly and positively correlated with the cell cycle-related genes, gene sets and cell cycle checkpoint genes (P < 0.01). Drug sensitivity analysis revealed that patients in the PKMYT1 high expression group had high sensitivity osimertinib, dabrafenib, carmustine and cediranib (P < 0.05). Mutation analysis revealed that the IDH1 gene had a higher mutation frequency in the PKMYT1 low expression group. The results of immune infiltration analysis showed that PKMYT1 expression was significantly positively correlated with glioma stroma score (r = 0.13, P < 0.001), immune score (r = 0.11, P < 0.01) and ESTIMATE score (r = 0.13, P < 0.001); and was significantly positively correlated with immune cell infiltration level of regulatory T (Treg) cells and M2-type macrophages (P < 0.05). Conclusion: Patients with high PKMYT1 expression have a poorer prognosis, and the mechanism may be related to tumor immune infiltration and cell cycle regulation. PKMYT1 is expected to be a potential target for the diagnosis and treatment of glioma.
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