Expression and prognostic value of glycolytic metabolism related protein methyltransferase-like 3 in resectable primary liver cancer / 中国医师进修杂志

ABSTRACT

Objective:To investigate the expression and prognostic value of glycolytic metabolism related methyltransferase-like 3 (METTL3) in resectable primary liver cancer.Methods:The METTL3 mRNA expression data, clinicopathological data and prognostic information of 364 patients with primary liver cancer and 50 healthy normal liver tissues were downloaded from the Cancer Genome Atlas (TCGA) database, and gene set enrichment analysis was performed. Then the tissue samples of 239 patients with primary liver cancer who underwent radical hepatectomy in Chongqing Armed Police Corps Hospital from January 2016 to may 2019 were selected. Among them, 110 cases contained matched normal liver tissue adjacent to the cancer. The expression of METTL3 protein was detected by immunohistochemical staining. Kaplan-Meier survival curve was drawn, and log-rank test was used for comparison; Cox proportional hazard model was used to evaluate the risk factors affecting the prognosis in patients with primary liver cancer.Results:TCGA database analysis result showed that the expression level of METTL3 mRNA in liver cancer tissue was significantly higher than that in normal liver tissue 3.72 (3.19, 4.03) vs. 2.45 (2.11, 2.68), and there was statistical difference ( P = 0.007); Kaplan-Meier survival curve analysis result showed that the median overall survival time and disease-free survival time in patients with high expression of METTL3 mRNA were significantly shorter than those in patients with low expression of METTL3 mRNA (43.0 months vs. 72.0 months and 22.0 months vs. 38.0 months, HR = 1.7 and 1.4, P = 0.002 and 0.024). Gene set enrichment analysis result showed that METTL3 mRNA was related to impaired glucose metabolism. In the clinical sample study, the positive expression rate of METTL3 protein in liver cancer tissue was significantly higher than that in normal liver tissue adjacent to cancer 54.55% (60/110) vs. 14.55% (16/110), and there was statistical difference ( χ2 = 38.92, P<0.01). Among 239 patients with primary liver cancer, 132 cases (55.23%) had positive expression of METTL3 protein in liver cancer tissue, and 107 cases had negative expression. Compared with METTL3 protein negative patients, METTL3 protein positive patients had higher body mass index; higher TNM stage, BCLC stage and tissue grade; more lesions; larger tumor sizes; more common satellite nodules; higher leukocyte count, platelet count and neutrophil count, and there were statistical differences ( P<0.05 or <0.01). Kaplan-Meier survival curve analysis result showed that the median overall survival time and disease-free survival time in patients with METTL3 protein positive were significantly shorter than those in patients with METTL3 negative (18.0 months vs. 38.0 months and 13.0 months vs. 27.0 months, P<0.01). Univariate and multivariate Cox analysis result showed that METTL3 protein positive in liver cancer tissue was an independent risk factor affecting overall survival time and disease-free survival time ( HR = 1.840 and 2.096, 95% CI 1.298 to 2.608 and 1.469 to 2.991, P<0.01). Conclusions:METTL3 is involved in glycolytic metabolism of primary liver cancer, and can be used as a promising biomarker to evaluate the prognosis of patients with primary liver cancer.