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LINE-1 hypomethylation is inversely correlated with UHRF1 overexpression in gastric cancer.

ABSTRACT: DNA methylation is an important epigenetic modification that alters gene expression; DNA hypomethylation contributes to tumorigenesis through multiple processes. In the present study, the methylation of long interspersed element-1 (LINE-1) in 95 gastric cancer (GC) tissues and matched adjacent normal tissues was investigated by pyrosequencing. LINE-1 methylation was compared with the expression of ubiquitin-like with PHD and ring-finger protein 1 (UHRF1), an essential regulator of DNA methylation, using reverse transcription-quantitative polymerase chain reaction. Significant hypomethylation of LINE-1 and overexpression of UHRF1 were observed in GC tissues compared with the matched controls (P<0.001 and P=0.001, respectively). LINE-1 hypomethylation was inversely correlated with UHRF1 overexpression in GC tissues (r=-0.026, P=0.028). In addition, LINE-1 hypomethylation in GC was significantly associated with Lauren's histological classification, tumor differentiation and background intestinal metaplasia (P=0.014, P=0.042 and P=0.034, respectively). These results suggest that LINE-1 hypomethylation may be a potential biomarker for GC and it is indirectly regulated by UHRF1 overexpression.

SUBMITTER: Hong JH

PROVIDER: S-EPMC5876460 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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LINE-1 hypomethylation is inversely correlated with UHRF1 overexpression in gastric cancer.

Hong Jang Hee JH Jin Eun-Heui EH Kim Soyeon S Song Kyu-Sang KS Sung Jae Kyu JK

Oncology letters 20180227 5

DNA methylation is an important epigenetic modification that alters gene expression; DNA hypomethylation contributes to tumorigenesis through multiple processes. In the present study, the methylation of long interspersed element-1 (LINE-1) in 95 gastric cancer (GC) tissues and matched adjacent normal tissues was investigated by pyrosequencing. LINE-1 methylation was compared with the expression of ubiquitin-like with PHD and ring-finger protein 1 (UHRF1), an essential regulator of DNA methylatio ...[more]

PMID: 29616129

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Project description:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer.One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (? 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman's correlation coefficient test. ?² test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer.Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively).KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.

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LINE-1 hypomethylation is inversely correlated with UHRF1 overexpression in gastric cancer.

Publications

LINE-1 hypomethylation is inversely correlated with UHRF1 overexpression in gastric cancer.

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