DNMT1 Overexpression Predicting Gastric Carcinogenesis, Subsequent Progression and Prognosis: a Meta and Bioinformatic Analysis

DNMT1 is important in maintaining DNA methylation, and participates in the oncogenesis via up- or down-regulation leading to hyper-methylation or hypo-methylation. In the meta and bioinformatic analysis, we found that DNMT1 expression was higher in gastric cancer, compared with normal ( < 0.00001), para-cancerous ( = 0.0004) and dysplasia ( < 0.00001) tissues. DNMT1 up-regulation was associated with gender (OR = 2.27, = 0.006), differentiation (OR = 0.21, = 0.01) and TNM stage (OR = 0.31, = 0.0005). Through TCGA database, DNMT1 overexpression increased gastric cancer risk, but unrelated with clinicopathological parameters and prognosis. Kaplan-Meier plotter showed, an increasing expression of DNMT1 was positive for overall survival rates of patients with stage III and IV ( = 0.044; = 0.047), N2 and N1-3 phases of lymph node metastasis ( = 0.023; = 0.032), as well as those with or without distant metastasis ( = 0.0052; = 0.021). For DNMT1 negative patients, the progression-free survival rates was better in patients with Her2+ or Her2- than positive ones ( = 0.00015; = 0.031). Besides, surgery alone was effective for the overall survival rates in patients with DNMT1 high expression ( = 0.035), while 5-Fu was useful for those with low expression ( < 0.05). In conclusion, these findings provided evidence that DNMT1 expression might be employed as a potential marker to indicate gastric carcinogenesis and subsequent progression, even prognosis.