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XRCC1 downregulated through promoter hypermethylation is involved in human gastric carcinogenesis
Author(s) -
WANG Ping,
TANG Jie Ting,
PENG Yan Shen,
CHEN Xiao Yu,
ZHANG Yan Jie,
FANG Jing Yuan
Publication year - 2010
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/j.1751-2980.2010.00459.x
Subject(s) - carcinogenesis , xrcc1 , dna methylation , methylation , cancer research , microbiology and biotechnology , cancer , bisulfite sequencing , biology , tissue microarray , promoter , gene expression , gene , genetics , single nucleotide polymorphism , genotype
OBJECTIVE: To analyze the expression and aberrant methylation of X‐ray repair cross‐complementing gene 1 (XRCC1) in gastric carcinogenesis, and identify the molecular mechanism of gastric carcinogenesis. METHODS: The method based on methyl binding domain protein (MBD) immuno‐precipitation and promoter microarray was employed to screen the gastric cancer‐related methylation‐sensitive gene. An immunohistochemistry assay was applied to detect the protein expression of XRCC1 in the multistep progression of gastric carcinogenesis. The mRNA expression of XRCC1 was determined by real‐time PCR in tumor tissues and their corresponding non‐tumorous tissues. The methylation status and Arg194Trp and Arg399Gln polymorphisms of XRCC1 in gastric cancer and gastritis tissues were analyzed by methylation‐specific PCR, bisulfite genomic sequencing and direct DNA sequencing, respectively. RESULTS: Promoter microarray screening and identification suggested that XRCC1 was a methylation‐sensitive gene. Immunochemistry results showed that XRCC1 protein expression gradually decreased with progression of gastric mucosal lesions ( P < 0.05). The positive rate of XRCC1 in patients with well/moderately differentiated gastric cancer was significantly higher than patients with poorly differentiated gastric cancer ( P < 0.05). The mRNA expression of XRCC1 in gastric cancer tissues was significantly lower than that in the non‐tumorous tissues ( P < 0.05). Meanwhile, XRCC1 methylation in gastric cancer tissues was more frequent than that in the gastritis tissues ( P < 0.05), and the downregulation of XRCC1 expression was relevant to methylation ( P < 0.05). CONCLUSION: The expression of XRCC1 is downregulated in gastric carcinogenesis, and promoter hypermethylation may be one of the mechanisms contributing to its downregulation.