DNMT1 overexpression predicting gastric carcinogenesis, subsequent progression and prognosis: a meta and bioinformatic analysis

Abstract

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.

Protein expression trends of DNMT1 in gastrointestinal diseases: From benign to precancerous lesions to cancer

“…When the aberrantly methylated occurs in the mammalian genome, DNMT1 will be transcribed in the nucleus with the expression gradually enhanced, promoting the advancement of DNA methylation and the procession of tumors[7]. Previously, we illustrated that the expression of DNMT1 was significantly higher in GC tissues than in non-GC tissues by meta-analysis[8]. Simultaneously, several studies have also revealed that DNMT1 was strongly expressed in GC and CRC[9,10], suggesting that DNMT1 could be a potential biomarker in screening of GI cancer.…”

Epigenetic Mechanisms in Gastric Cancer: Potential New Therapeutic Opportunities

“…Mutze et al found that low DNMT1 expression predicted better OS and clinical response in 127 patients treated with adjuvant therapy [ 83 ], and a comprehensive meta-analysis found that tumor tissues are characterized by high expression levels of DNMT1, with respect to normal, para-cancerous, and dysplastic tissues. Moreover, DNMT1 was found upregulated in stage III and IV patients, associated with GC risk and worse prognosis [ 84 ]. Accordingly, the TCGA molecular classification identified DNMT1 as the most upregulated among all DNMTs in each molecular subgroup [ 41 ], suggesting that it could be a common molecular driver for different pathogenesis patterns.…”

Quantum microRNA network analysis in gastric and esophageal cancers: Xenotropic plant microRNAs cure from cancerous paradox via Helicobacter pylori infection

“…Although basic helix-loop-helix transcription factor 38 (TWIST1) expression high was implicated in positive proliferation of gastric cancer cell [47] and DNA methyltransferase 1 (DNMT1) expression was higher in gastric cancer than normal, para-cancerous and dysplasia tissues in the bioinformatic meta-analysis [48]. TWIST expression was suppressed by miR-151a-3p upregulation with miR-539-5p (Figure 2A and 3A) and DNMT1 is also blocked by miR-148a-3p upregulation with miR-185-5p, miR-152-3p, miR-126-3p and miR-140-5p (Figure 2A).…”