Structural maintenance of chromosome 4 gene expression in glioma and its clinical significance / 中华神经医学杂志

ABSTRACT

Objective:To analyze the expression of structural maintenance of chromosome 4( SMC4) gene in glioma and its clinical significance. Methods:(1) The SMC4 mRNA expression data of 749 glioma tissues and clinical data of these glioma patients were downloaded from Chinese Glioma genome Atlas (CGGA) database. Univariate Cox analysis and multivariate Cox analysis were used to analyze the independent influencing factors for poor prognosis in patients with glioma. Patients were divided into high SMC4 mRNA expression group and low SMC4 mRNA expression group; Kaplan-Meier method was used to draw the survival curve of these patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of SMC4 mRNA in 1-, 3- and 5-year survival of these patients. (2) The relationships between SMC4 mRNA expression levels in glioma tissues from cancer Genome Atlas (TCGA) database and overall survival of these glioma patients were analyzed by gene expression profiling interactive analysis (GEPIA). The SMC4 protein expressions in high-grade glioma (glioblastoma) and low-grade glioma were determined by human protein atlas (HPA) online database. (3) Genomic enrichment analysis was used to analyze and compare the differences of gene body (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in gliomas between SMC4 mRNA high expression group and SMC4 mRNA low expression group. Co-expression analysis was performed to analyze the genes related to SMC4 mRNA. Results:(1) Multivariate Cox analysis showed that SMC4 mRNA ( HR=1.314, 95%CI: 1.209-1.428, P=0.000), glioma primary-recurrent-secondary (PRS) type, glioma WHO grading, age, chemotherapy, isocitrate dehydrogenase ( IDH) mutation and 1P/19q deletion were independent influencing factors for poor prognosis of glioma patients. Survival analysis showed that the overall survival of patients with low SMC4 mRNA expression was significantly higher than that of patients with high SMC4 mRNA expression ( P<0.05). The area under the curve (AUC) of ROC was 0.712, 0.784 and 0.791, respectively, in predicting 1-year survival rate, 3-year survival rate and 5-year survival rate. (2) SMC4 mRNA expressions in low-grade and high-grade gliomas were statistically lower than those in normal control brain tissue ( P<0.05). The overall survival of low-grade glioma patients with low SMC4 mRNA expression was significantly higher than that of patients with SMC4 mRNA high expression ( P<0.05). There was no significant difference in overall survival between high-grade glioma patients with low SMC4 mRNA expression and high SMC4 mRNA expression ( P>0.05). The SMC4 protein expression in low-grade glioma was significantly higher than that in high-grade glioma. (3) Genome enrichment analysis showed that GO enriched in gliomas with high SMC4 mRNA expression was about nuclear chromosome aggregation, protein complex driving, cell cycle meiotic and process of meiotic cell cycle. KEGG enrichment included cell cycle, DNA replication, mismatch repair, P53 signaling pathway, pancreatic cancer and other related pathways. Gene co-expression analysis showed that the first 5 genes, including BUB1, WEE1, CENPL, KIF23 and SGOL2, were positively correlated with SMC4 mRNA expression; and the first 5 genes, including FBXW4, PNMAL2, MATK, PASL10A and CTD-2210P24.4, were negatively correlated with SMC4 mRNA expression. Conclusions:Glioma patients with SMC4 mRNA high expression have poor prognosis. As a high risk factor, SMC4 mRNA can be used as an independent prognostic indicator of glioma patients, and its biological function is related to DNA replication of glioma.