Relationship between enhancer of zeste homolog 2 mRNA level and prognosis of gastric cancer patients / 肿瘤研究与临床

ABSTRACT

Objective:To analyze the correlation between enhancer of zeste homolog 2 (EZH2) mRNA expression level and prognosis of patients with gastric cancer.Methods:The differences of the EZH2 mRNA levels between gastric cancer tissues and adjacent normal tissues and among patients with different clinical stages were analyzed by The Cancer Genome Atlas (TCGA) database. According to the median expression level of EZH2 mRNA (5.59), 368 patients were divided into high expression group (184 cases) and low expression group (184 cases). Kaplan-Meier method was used to analyze the relationship between EZH2 mRNA expression level and overall survival (OS) of patients. Multivariate Cox regression model was used to analyze the relationship between age, clinical stage, TNM stage, gender, EZH2 mRNA expression level and OS. The relationships between EZH2 mRNA expression level and OS in all gastric cancer patients, human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative patients were analyzed by KM-plotter online database. The KEGG pathway enrichment analysis of tumor samples from TCGA-STAD collection in the TCGA database was carried out by using GSEA software, and enrichment score (ES), normalized enrichment score (NES), nominal P value (NOM p-val) and multiple testing correction (FDR q-val) were calculated. KEGG pathways related to tumorigenesis were screened according to FDR q-val < 0.25. Results:Among 375 cases of gastric cancer tissues in the TCGA database, the level of EZH2 mRNA in 171 cases were low and the level of EZH2 mRNA in 204 cases were high; the level of EZH2 mRNA in 32 cases of adjacent normal tissues were low. The median EZH2 mRNA expression level in adjacent normal tissues was 1.73, and the median EZH2 mRNA expression level in tumor tissues was 5.59. The expression level of EZH2 mRNA in gastric cancer tissues was higher than that in normal adjacent tissues, and the difference was statistically significant ( u = 925, P < 0.05). There was no significant difference in EZH2 mRNA expression level between patients with different clinical stages ( DF = 3, P = 0.25). Kaplan-Meier analysis showed that patients with high expression of EZH2 mRNA had longer OS time than those with low expression of EZH2 mRNA ( HR = 0.623, P = 0.008). Univariate Cox analysis showed that EZH2 mRNA level was one of the independent risk factors for OS in patients ( HR = 0.666, P = 0.024). In the KM-plotter database, patients with high expression of EZH2 mRNA (632 cases) had longer OS time than patients with low expression of EZH2 mRNA (244 cases) ( HR = 0.75, P = 0.002). In patients with positive HER2 (344 cases), patients with high expression of EZH2 mRNA had a shorter OS time ( HR = 1.31, P = 0.042), while in patients with negative HER2 (532 cases), patients with low expression of EZH2 mRNA had a shorter OS time ( HR = 0.57, P < 0.05). GSEA enrichment found that EZH2 mRNA was related to a variety of tumor-related pathways and cell synthesis and metabolism pathways. Conclusion:The expression of EZH2 mRNA is related to the prognosis of patients with gastric cancer, and it may be used as a biomarker for evaluating the prognosis of patients with gastric cancer.