DNMT1 overexpression predicting gastric carcinogenesis, subsequent progression and prognosis: a meta and bioinformatic analysis
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Tianmiao Ma1,2, Hao Li1, Mingjun Sun2, Yuan Yuan1 and Li-Ping Sun1
1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Liaoning Provincial Education Department, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Shenyang, Liaoning, China
2Digestive Department, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
Li-Ping Sun, email: firstname.lastname@example.org
Yuan Yuan, email: email@example.com
Keywords: DNMT1, gastric cancer, meta-analysis, bioinformatic analysis
Received: August 02, 2017 Accepted: September 20, 2017 Published: October 04, 2017
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 (p < 0.00001), para-cancerous (p = 0.0004) and dysplasia (p < 0.00001) tissues. DNMT1 up-regulation was associated with gender (OR = 2.27, p = 0.006), differentiation (OR = 0.21, p = 0.01) and TNM stage (OR = 0.31, p = 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 (P = 0.044; P = 0.047), N2 and N1-3 phases of lymph node metastasis (P = 0.023; P = 0.032), as well as those with or without distant metastasis (P = 0.0052; P = 0.021). For DNMT1 negative patients, the progression-free survival rates was better in patients with Her2+ or Her2- than positive ones (P = 0.00015; P = 0.031). Besides, surgery alone was effective for the overall survival rates in patients with DNMT1 high expression (P = 0.035), while 5-Fu was useful for those with low expression (P < 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.
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