Expression and clinical significant of pyruvate dehydrogenase kinase 1 in gliomas based on the Cancer Genome Atlas by bioinformatics analysis

Objective To investigate the molecular and clinical features of PDK1 (pyruvate dehydrogenase kinase 1) in gliomas based on the Cancer Genome Atlas (TCGA) by bioinformatics analysis. Methods The clinical data of 641 glioma patients in TCGA database were retrospectively analyzed. The online analysis website of GEPIA (http: //gepia.cancer-pku.cn/) was used to analyze PDK1 expression in glioma patients. Pearson correlation analysis was performed to create a gene list related to PDK1. The online analysis tool STRING was used to analyze the interaction network of the differential genes. According to the degree of confidence, the top key proteins were screened. The function of PDK1-related differential genes and its relationship with the kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were explored by gene ontology (GO) analysis. According to PDK1 protein expression, all patients were divided into PDK1 protein low expression group (380 cases) and PDK1 protein high expression group (261 cases). Kaplan-Meier survival curves were used to compare the survival differences between the two groups of patients. Univariate and multivariate Cox regression analysis were used to determine the effect of PDK1 protein expression on the prognosis of patients with glioma. Results The expression of PDK1 protein in 641 glioma patients in TCGA database showed that the expression level in the World Health Organization(WHO) Ⅳ glioma (8.86±0.90) was higher than that in grade Ⅱ (7.24±0.60) and grade Ⅲ (7.34±0.80)(P 0.05). The cumulative survival rate of glioma patients in the PDK1 high-expression group was significantly lower than that in the PDK1 low-expression group (P<0.05). Pearson correlation test analysis revealed that 96 genes were closely related to PDK1 expression, of which 69 were positively correlated and 27 were negatively correlated. GO analysis and KEGG pathway analysis showed that PDK1 participated in many important biological processes, which were closely related to the hypoxia microenvironment, reaction to organic cyclic compounds, reaction to organic nitrogen compounds, response to cAMP and the HIF-1 signaling pathway. Multivariate analysis showed that age (HR=1.579, 95% CI: 1.085-2.299, P=0.017), WHO grade (HR=12.106, 95% CI: 6.521-22.474, P<0.001) and radiotherapy (HR=0.502, 95% CI: 0.325-0.775, P=0.002) were independent influencing factors for the survival of glioma patients (all P <0.05) and could be used independently to explore the prognosis of patients.However, PDK1 protein expression does not affect the prognosis of glioma patients. Conclusion PDK1 expression is different in glioma patients with different WHO pathological levels, and mainly related to hypoxia and HIF-1 signaling pathway. Key words: Glioma; Prognosis; The cancer genome atlas; Pyruvate dehydrogenase kinase 1