Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (3): 76-84.doi: 10.6040/j.issn.1671-7554.0.2024.0670

• Clinical Medicine • Previous Articles    

Role of GPR133 gene methylation in predicting lymph node metastasis in early gastric cancer

ZHANG Jie1, ZHAO Yinghui2, DONG Yaqi1, LI Juan1, LI Peilong1, DU Lutao1,2   

  1. 1. Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    2. Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2025-04-08

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Abstract: Objective To explore the clinical value of quantitatively detecting methylation sites in the GPR133 gene for predicting lymph node metastasis(LNM)in early gastric cancer. Methods This retrospective study included 100 patients with T1 stage gastric cancer treated at the Department of Gastroenterology, Second Hospital of Shandong University, from January 2023 to May 2024. The MethylationEPIC array was used to analyze the whole-genome methylation status of surgical tissue samples from LNM-positive and LNM-negative patients, so as to identify differentially methylated positions(DMPs). Candidate DMPs were determined based on gene enrichment analysis and functional prediction. Pyrosequencing was performed on FFPE sections from 20 LNM-positive and 80 LNM-negative patients to validate the methylation levels of candidate DMPs. The clinical value of DMPs in diagnosing early gastric cancer lymph node metastasis was assessed using the area under the receiver operating characteristic curve(AUC). Results MethylationEPIC array analysis revealed a specific methylation pattern in T1 stage gastric cancer LNM-positive samples. Using a threshold of |Δβ|≥0.1 and P<0.01, a total of 1,794 DMPs were initially identified. According to the results of gene matching and TCGA database analysis and cAMP binding pathway enrichment, cg00633768 on GPR133 gene was identified as a candidate site. Pyrosequencing results showed that cg00633768 methylation level could significantly distinguish between LNMS positive and negative samples(AUC=0.869, sensitivity=64.3%, specificity=100%, cut-off value=0.618 9). Conclusion The methylation level of cg00633768 in the GPR133 gene is significantly higher in LNM-positive patients compared to LNM-negative patients. This site has substantial clinical value for predicting lymph node metastasis in early gastric cancer.

Key words: Early gastric cancer, Lymph node metastasis, Methylation, G-protein coupled receptor, GPR133

CLC Number: 

  • R735.2
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