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Updated: Jun 6, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
XRCC1 downregulated through promoter hypermethylation is involved in human gastric carcinogenesis
Ping Wang1, Jie Ting Tang, Yan Shen Peng
1Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China.
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.
Insights
X-ray repair cross-complementing gene 1 (XRCC1) expression decreases during gastric carcinogenesis. Promoter hypermethylation is identified as a key mechanism contributing to this XRCC1 downregulation in stomach cancer development.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Gastric cancer is a significant global health concern.
- Understanding the molecular mechanisms underlying gastric carcinogenesis is crucial for developing effective diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the expression patterns and methylation status of X-ray repair cross-complementing gene 1 (XRCC1) in gastric carcinogenesis.
- To elucidate the role of XRCC1 alterations in the molecular pathogenesis of gastric cancer.
Main Methods:
- Utilized methyl binding domain protein (MBD) immunoprecipitation and promoter microarray to identify methylation-sensitive genes.
- Assessed XRCC1 protein and mRNA expression via immunohistochemistry and real-time PCR.
- Analyzed XRCC1 methylation status and polymorphisms using methylation-specific PCR, bisulfite sequencing, and direct DNA sequencing.
Main Results:
- XRCC1 was identified as a methylation-sensitive gene.
- XRCC1 protein and mRNA expression significantly decreased with gastric carcinogenesis progression.
- Increased XRCC1 methylation was observed in gastric cancer tissues, correlating with its downregulation.
Conclusions:
- XRCC1 expression is significantly downregulated during gastric carcinogenesis.
- Promoter hypermethylation is a key molecular mechanism contributing to XRCC1 downregulation in gastric cancer.
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