Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (6): 26-34.doi: 10.6040/j.issn.1671-7554.0.2021.0110

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Value of abnormal methylation of cg16212145 on GZMB gene in early screening of gastric cancer

WANG Jing1,2, XIE Yan1,2, LI Peilong1,2, DU Lutao1,2, WANG Chuanxin1,2   

  1. 1. Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong, China;
    2. Tumor Marker Detection Engineering Laboratory of Shandong Province, Jinan 250033, Shandong, China
  • Published:2022-06-17

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Abstract: Objective To obtain the specific genome-wide methylation profile of gastric cancer derived from peripheral blood mononuclear cells(PBMC), and to explore the clinical value of methylation points derived from PBMC in the early diagnosis of gastric cancer. Methods The genome-wide DNA methylation status of PBMC in 20 gastric cancer patients and 20 healthy controls was detected with Methylation850 BeadChip. The gastric cancer-specific methylation profile was constructed and differentially methylated points(DMPs)were obtained. Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the genes where DMPs were located for functional prediction. Statistical screening of DMPs was performed using a random forest-based multi-factor filtering method. Next-generation sequencing-based multiplex target region methylation enrichment sequencing was performed on 34 patients with stage I gastric cancer and 21 healthy controls to verify the selected DMPs. Results The results of methylation BeadChip showed PBMC from gastric cancer patients had unique genome-wide methylation profile. A total of 5 883 DMPs were obtained with |Δβ|>0.06 and adjust P<0.05 as pre-screening conditions, including 2 513 hypermethylated sites and 3 370 hypomethylated sites. GO analysis and KEGG analysis showed that 2 677 genes where 5 883 DMPs were located were mainly associated with MAPK signaling pathway and transcriptional dysregulation in cancer. Granzyme B(GZMB)gene cg16212145 was hypermethylated in PBMC of gastric cancer patients, and the difference was statistically significant(Δβ=0.0807, adjust P=0.001). The results of multiple target region methylation enrichment sequencing showed that abnormal methylation status of CpG site cg16212145 could distinguish patients with stage I gastric cancer from healthy controls(AUC=0.807, P<0.001). Conclusion Gastric cancer patients have a specific genome-wide methylation profile derived from PBMC. The GZMB gene cg16212145 exhibits high methylation status in PBMC of gastric cancer patients, which has important clinical value in the early screening of gastric cancer.

Key words: Gastric cancer, DNA methylation, Peripheral blood mononuclear cell, Early screening, Markers

CLC Number: 

  • R735.2
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